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系統識別號 U0026-1810201217444400
論文名稱(中文) 利用比較性蛋白質體分析方法找出肺癌轉移相關之分泌蛋白質
論文名稱(英文) Identification of Lung Cancer Metastasis-Associated Proteins using Comparative Secretome Analysis
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 101
學期 1
出版年 101
研究生(中文) 張盈華
研究生(英文) Ying-Hua Chang
學號 tb8971060
學位類別 博士
語文別 英文
論文頁數 135頁
口試委員 指導教授-廖寶琦
口試委員-王憶卿
口試委員-鄭宏祺
口試委員-洪澤民
口試委員-余兆松
口試委員-賴建成
中文關鍵字 肺癌  分泌蛋白質體  非標定定量蛋白質體  轉移 
英文關鍵字 Lung cancer  secretome  label-free quantitative proteomics  metastasis 
學科別分類
中文摘要 轉移為成功治療肺癌的主要障礙。癌細胞分泌蛋白質會促使轉移的進展,特別是在癌細胞欲展現遷移及侵襲性能的期間。為了尋找癌細胞中增進轉移之分泌蛋白質,我們使用了膠集電泳輔助之純化方式結合非標記定量蛋白質體技術,藉此比較兩種不同轉移潛力之肺腺癌細胞株CL1-0(低侵入能力)與CL1-5(高侵入能力)中分泌蛋白質體的差異。透過比較,我們鑑定出660個蛋白質,其中有69個蛋白質在兩細胞株中被認定具有差異性表現,經文獻篩選,FN1, TIMP1, 與A1AT為具較高侵入能力CL1-5細胞株中其分泌表現量較高之蛋白質進一步深入探討其在肺腺癌轉移調控過程所扮演之角色。藉分子和病理驗證闡明FN1 、TIMP1及A1AT表現量之改變與肺腺癌之轉移潛力相關。當三者之表現量及分泌量降低時,CL1-5之遷移及侵襲能力下降;反之,當三者過度的表現及分泌時,在CL1-0有能力提升的現象。此外,在過去乳癌研究中發現,癌細胞會藉由聚合細胞表面纖維連接蛋白質(FN1)來附著肺毛細血管內皮細胞上之細胞表面受體DPP IV而促使癌細胞轉移至肺臟,本研究發現細胞表面聚合纖維連接蛋白質在懸浮型CL1-5細胞表面較CL1-0來得高。根據此項發現,當內源性之FN1、TIMP1及A1AT蛋白質表現量降低時,其懸浮型CL1-5細胞表面聚合之纖維連接蛋白質表現量與癌細胞肺移入量皆會受到抑制。本實驗說明結合定量蛋白質體分析與不同轉移能力的癌細胞分泌蛋白質研究,提供新的機會進行有效率地鑑定與促使癌轉移相關分泌蛋白質。
英文摘要 Metastasis is a major obstacle that must be overcome for the successful treatment of lung cancer. Proteins secreted by cancer cells may facilitate the progression of metastasis, particularly during the phases of migration and invasion. To discover metastasis-promoting secretory proteins within cancer cells, we used the stacking gel-aided purification method along with the label-free quantitative proteomics approach to compare secretomes from the lung adenocarcinoma cell lines CL1-0 and CL1-5, which exhibit low and high metastatic properties, respectively. By employing quantitative analyses, we identified 660 proteins, 69 of which were considered to be expressed at different levels between the two cell lines. High levels of FN1, TIMP1, and A1AT were secreted by CL1-5, and the roles of each were investigated for their influence on lung adenocarcinoma metastasis. Molecular and pathological confirmation demonstrated that altered expression of FN1, TIMP1, and A1AT correlates with the metastatic potential of lung adenocarcinoma. The migration and invasion properties of CL1-5 cells were significantly diminished by reducing the expression and secretion of these three proteins. Conversely, the migration and invasion properties of CL1-0 cells were significantly increased through the over-expression and secretion of FN1, TIMP1, and A1AT. Furthermore, the assembly levels of the metastasis-promoting pericellular fibronectin (FN1), which facilitates colonization of lung capillary endothelia by adhering to the cell surface receptor DPP IV, were higher on the surfaces of suspended CL1-5 cells than on those of the CL1-0 cells. This discovery reflects previous findings in breast cancer. In line with this finding, FN1 assembly and the lung colonization of suspended CL1-5 cells were inhibited when endogenous FN1, TIMP1, and A1AT proteins were knocked down using siRNA. The major thrust of this study is to demonstrate the effects of coupling the label-free proteomics strategy with the secretomes of cancer cells that differentially exhibit invasive and metastatic properties. This provides a new opportunity for the effective identification of metastasis-associated proteins that are secreted by cancer cells and promote experimental metastasis.
論文目次 CONTENTS

1 RESEARCH BACKGROUND ---------------------------------------------------------------- page 1-7
1.1 Lung Cancer ---------------------------------------------------------------------------- page 1
1.2 Lung Cancer Metastasis ------------------------------------------------------------- page 2
1.3 Role of Secretome in Metastasis ----------------------------------------------- page 2-4
1.4 Quantitative Proteomics Approaches --------------------------------------- page 4-6
1.5 Significance of This Research ---------------------------------------------------- page 6-7
2 RESEARCH GOALS ------------------------------------------------------------------------- page 8-9
3 MATERIALS AND METHODS ---------------------------------------------------------- page 10-20
3.1 Experimental Design --------------------------------------------------------------- page 10
3.2 Cell Culture and Conditioned Medium Harvest ------------------------------ page 11
3.3 Exosome Purification ----------------------------------------------------------- page 11-12
3.4 Stacking Gel-aided Purification -------------------------------------------------- page 12
3.5 In-gel Digestion ------------------------------------------------------------------ page 12-13
3.6 nanoLC-MS/MS Analysis ------------------------------------------------------ page 13-14
3.7 Peptide/protein Quantification and Identification ---------------------- page 14-15
3.8 Western Blot --------------------------------------------------------------------- page 15-16
3.9 Tissue Microarray (TMA) and Immunohistochemistry (IHC) --------- page 16-17
3.10 Gene Knockdown by Small Interfering RNA (siRNA) ---------------------- page 17
3.11 Gene Over-expression by Plasmid DNA ---------------------------------- page 17-18
3.12 MTT Assay --------------------------------------------------------------------------- page 18
3.13 Wound Healing Assay ------------------------------------------------------------- page 18
3.14 Transwell Migration Assay ------------------------------------------------------- page 19
3.15 Matrigel Invasion Assay ---------------------------------------------------------- page 19
3.16 Flow Cytometry ---------------------------------------------------------------- page 19-20
3.17 Lung Colony Assay ----------------------------------------------------------------- page 20
3.18 Statistical Analysis ----------------------------------------------------------------- page 20
4 RESULTS ------------------------------------------------------------------------------------ page 21-31
4.1 Cell Conditioned Media Influences Lung Adenocarcinoma Cell Migration and Invasion ------------------------------------------------------------------------------------- page 21
4.2 Monitoring the Quality of CM Samples ----------------------------------- page 21-22
4.3 Establishment of Cell Secretome Analyses Using Stacking Gel-aided Purification Combined with Label-free Quantitative Proteomics to Identify Metastasis-associated Proteins in Lung Adenocarcinoma Cells ---------------------------------------- page 22-25
4.4 Profiling of the Identified Proteins ------------------------------------------ page 25-27
4.5 Confirmation of Target Protein Expression Levels in CM via Western Blot ------------------------------------------------------------------------------------------------ pag 27-28
4.6 Target Protein Expression Levels in Clinical Tissue Specimens of Lung Adenocarcinoma Patients -------------------------------------------------------------- page 28
4.7 A1AT, TIMP1, and FN1 Do Not Influences Lung Adenocarcinoma Cancer Cell Proliferation --------------------------------------------------------------------------- page 29
4.8 A1AT, TIMP1, and FN1 Promote Cancer Migration and Invasion --------------------------------------------------------------------------------------------------- page 29
4.9 A1AT, TIMP1, and FN1 Influences the Assembly of Pericellular Polymeric FN on Suspended CL1-5 Lung Adenocarcinoma Cells and Promotes their Abilities to Colonize the Lung -------------------------------------------------------------------- page 30-31
5 Discussion --------------------------------------------------------------------------------- page 32-41
6 Conclusion ------------------------------------------------------------------------------------- page 42
7 References -------------------------------------------------------------------------------- page 43-60
8 Tables --------------------------------------------------------------------------------------- page 61-67
9 Figures -------------------------------------------------------------------------------------- page 68-92
10 Appendices ---------------------------------------------------------------------------- page 93-134
Appendix 1: Quantified BSA Peptides List ------------------------------------- page 93-96
Appendix 2: 660 Quantified Proteins List ------------------------------------ page 97-129
Appendix 3: 68 Proteins with Differentially Expressed Levels between CL1-0 and CL1-5 Based on Multiple Hypothesis Tests --------------------------------- page 130-134
11 PUBLICATION LIST ------------------------------------------------------------------------ page 135
參考文獻 Al Bugami, M. M.; Farahat, K. L.; Al-Ashgar, H. I.; Hainau, B. Fibrolamellar hepatocellular carcinoma with alpha-one antitrypsin liver disease. Saudi J Gastroenterol 10(2):92-95. 2004.

Aljada, I.S.; Ramnath, N.; Donohue, K.; Harvey, S.; Brooks, J.J.; Wiseman, S.M.; Khoury, T.; Loewen, G.; Slocum, H.K.; Anderson, T.M.; Bepler, G.; Tan, D. Upregulation of the tissue inhibitor of metalloproteinase-1 protein is associated with progression of human non-small-cell lung cancer. J Clin Oncol. 22(16), 3218-3229. 2004.

Anderson, N. L.; Polanski, M.; Pieper, R.; Gatlin, T.; Tirumalai, R. S.; Conrads, T. P.; Veenstra, T. D.; Adkins, J. N.; Pounds, J. G.; Fagan, R.; Lobley, A. The human plasma proteome: a nonredundant list developed by combination of four separate sources. Mol Cell Proteomics 3:311-326. 2004.

Andre, F.; Schartz, N. E.; Movassagh, M.; Flament, C.; Pautier, P.; Morice, P.; Pomel, C.; Lhomme, C.; Escudier, B.; Le Chevalier, T.; Tursz, T.; Amigorena, S.; Raposo, G.; Angevin, E.; Zitvogel, L. Malignant effusions and immunogenic tumour-derived exosomes. Lancet 360:295-305. 2002.

Astrof, S.; Hynes, R. O. Fibronectins in vascular morphogenesis. Angiogenesis 12(2):165-175. 2009.

Atlanta: American Cancer Society: 2012. American Cancer Society 2012.

Aziz, M. H.; Hafeez, B. B.; Sand, J. M.; Pierce, D. B.; Aziz, S. W.; Dreckschmidt, N. E.; Verma, A. K. Protein kinase Cvarepsilon mediates Stat3Ser727 phosphorylation, Stat3-regulated gene expression, and cell invasion in various human cancer cell lines through integration with MAPK cascade (RAF-1, MEK1/2, and ERK1/2). Oncogene 29(21):3100-3109. 2010.

Bantscheff, M.; Lemeer, S.; Savitski, M. M.; Kuster, B. Quantitative mass spectrometry in proteomics: critical review update from 2007 to the present. Anal Bioanal Chem 404(4):939-965. 2012.

Bendtsen, J. D.; Jensen, L. J.; Blom, N.; Von Heijne, G.; Brunak, S. Feature based prediction of non-classical and leaderless protein secretion. Protein Eng Des Sel 17:349-356. 2004.

Blanco, M. A.; Leroy, G.; Khan, Z.; Alečković, M.; Zee, B. M.; Garcia, B. A.; Kang, Y. Global secretome analysis identifies novel mediators of bone metastasis. Cell Res 22(9):1339-1355. 2012.

Bondarenko, P. V.; Chelius, D.; Shaler, T. A. Identification and Relative Quantitation of Protein Mixtures by Enzymatic Digestion Followed by Capillary Reversed-Phase Liquid Chromatography−Tandem Mass Spectrometry. Anal Chem 74:4741-4749. 2002.

Böttger, A.; Strasser, D.; Alexandrova, O.; Levin, A.; Fischer, S.; Lasi, M.; Rudd, S.; David, C. N. Genetic screen for signal peptides in Hydra reveals novel secreted proteins and evidence for non-classical protein secretion. Eur J Cell Biol 85: 1107-1117. 2006.

Boucaut, J. C.; Darribere, T. Presence of fibronectin during early embryogenesis in amphibian Pleurodeles waltlii. Cell Differ 12(2):77-83. 1983.

Chang, C. C.; Shih, J. Y.; Jeng, Y. M.; Su, J. L.; Lin, B. Z.; Chen, S. T.; Chau, Y. P.; Yang, P. C.; Kuo, M. L. Connective tissue growth factor and its role in lung adenocarcinoma invasion and metastasis. J. Natl. Cancer Inst. 96:364-375. 2004.

Chang, Y. H.; Wu, C. C.; Chang, K. P.; Yu, J. S.; Chang, Y. C.; Liao, P. C. Cell secretome analysis using hollow fiber culture system leads to the discovery of CLIC1 protein as a novel plasma marker for nasopharyngeal carcinoma. J Proteome Res 8: 5465-5474. 2009.

Chelius, D.; Bondarenko, P. V. Quantitative Profiling of Proteins in Complex Mixtures Using Liquid Chromatography and Mass Spectrometry. J Proteome Res 1:317-323. 2002.

Cheng, H. C.; Abdel-Ghany, M.; Elble, R. C.; Pauli, B. U. Lung endothelial dipeptidyl peptidase IV promotes adhesion and metastasis of rat breast cancer cells via tumor cell surface-associated fibronectin. J Biol Chem 273:24207-24215. 1998.

Cheng, H. C.; Abdel-Ghany, M.; Pauli, B. U. A novel consensus motif in fibronectin mediates dipeptidyl peptidase IV adhesion and metastasis. J Biol Chem 278:24600-24607. 2003.

Chirco, R.; Liu, X. W.; Jung, K. K.; Kim, H. R. Novel functions of TIMPs in cell signaling. Cancer Metastasis 25(1):99-113. 2006.

Chiu, K. H.; Chang, Y. H.; Wu, Y. S.; Lee, S. H.; Liao, P. C. Quantitative secretome analysis reveals that COL6A1 is a metastasis-associated protein using stacking gel-aided purification combined with iTRAQ labeling. J Proteome Res 10(3): 1110-1125. 2011.

Choi, Y.J.; Shin, D.Y.; Lee, Y.W.; Cho, C.K.; Kim, G.Y.; Kim, W.J.; Yoo, H.S.; Choi, Y.H. Inhibition of cell motility and invasion by HangAmDan-B in NCI-H460 human non-small cell lung cancer cells. Oncol Rep. 6(6), 1601-1608. 2011.

Chu, Y.W.; Yang, P.C.; Yang, S.C.; Shyu, Y.C.; Hendrix, M.J.; Wu, R.; Wu, C.W. Selection of invasive and metastatic subpopulations from a human lung adenocarcinoma cell line. Am J Respir Cell Mol Biol. 17(3), 353-360. 1997.

Clark, E. A.; Golub, T. R.; Lander, E. S.; Hynes, R. O. Genomic analysis of metastasis reveals an essential role for RhoC. Nature 406(6795):532-535. 2000.

Clayton, A.; Mason, M. D. Exosomes in tumour immunity Curr Oncol 16:46-49. 2009.
Comunale, M. A.; Rodemich-Betesh, L.; Hafner, J.; Wang, M.; Norton, P.; Di Bisceglie, A. M.; Block, T.; Mehta, A. Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma. PLoS One 5(8):e12419. 2010.

Connors, W. L.; Jokinen, J.; White, D. J.; Puranen, J. S.; Kankaanpää, P.; Upla, P.; Tulla, M.; Johnson, M. S.; Heino, J. Two synergistic activation mechanisms of alpha2beta1 integrin-mediated collagen binding. J Biol Chem 282(19):14675-14683. 2007.

Cox, G.; Jones, J.; O’Byrne, K. Matrix metalloproteinase 9 and the epidermal growth factor signal pathway in operable non-small cell lung cancer. Clin Cancer Res 6:2349-2355. 2000.

Darnell, J. E. Jr. STATs and gene regulation. Science 277(5332):1630-1635. 1997.
Deryugina, E. I.; Quigley, J. P. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25: 9-34. 2006.

Donnini, S.; Monti, M.; Castagnini, C.; Solito, R.; Botta, M.; Schenone, S.; Giachetti, A.; Ziche, M. Pyrazolo-pyrimidine-derived c-Src inhibitor reduces angiogenesis and survival of squamous carcinoma cells by suppressing vascular endothelial growth factor production and signaling. Int J Cancer 120(5):995-1004. 2007.

Dubinett, S. M.; Elashoff, D.; Meyerson, M. Assessing prognosis in non-small-cell lung cancer: avenues to a more complete picture? J Clin Oncol 22(16):3209-3211. 2004.

Egeblad, M.; Werb, Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3):161-174. 2002.

El-Akawi, Z. J.; Al-Hindawi, F. K.; Bashir, N. A. Alpha-1 antitrypsin (alpha1-AT) plasma levels in lung, prostate and breast cancer patients. Neuro Endocrinol Lett 29(4):482-484. 2008.

El-Akawi, Z. J.; Abu-Awad, A. M.; Sharara, A. M.; Khader, Y. The importance of alpha-1 antitrypsin (alpha1-AT) and neopterin serum levels in the evaluation of non-small cell lung and prostate cancer patients. Neuro Endocrinol Lett 31(1):113-116. 2010.

Eun, D. W.; Ahn, S. H.; You, J. S.; Park, J. W.; Lee, E. K.; Lee, H. N.; Kang, G. M.; Lee, J. C.; Choi, W. S.; Seo, D. W.; Han, J. W. PKCepsilon is essential for gelsolin expression by histone deacetylase inhibitor apicidin in human cervix cancer cells. Biochem Biophys Res Commun 354(3):769-775. 2007.

Friedl, P.; Wolf, K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3:362-374. 2003.

Fong, K.M.; Kida, Y.; Zimmerman, P.V.; Smith, P.J. TIMP1 and adverse prognosis in non-small cell lung cancer. Clin Cancer Res. 2(8), 1369-1372. 1996.

Garber, K. Epithelial-to-mesenchymal transition is important to metastasis, but questions remain. J Natl Cancer Inst 100:232-239. 2008.

Gettins, P. G. Serpin structure, mechanism, and function. Chem Rev 102(12):4751-4804. 2002.

Gilchrist, A.; Au, C. E.; Hiding, J.; Bell, A. W.; Fernandez-Rodriguez, J.; Lesimple, S.; Nagaya, H.; Roy, L.; Gosline, S. J.; Hallett, M.; Paiement, J.; Kearney, R. E.; Nilsson, T.; Bergeron, J. J. Quantitative proteomics analysis of the secretory pathway. Cell 127:1265-1281. 2006.

Gillan, L.; Matei, D.; Fishman, D. A.; Gerbin, C. S.; Karlan, B. Y.; Chang, D. D. Periostin secreted by epithelial ovarian carcinoma is a ligand for alpha(V)beta(3) and alpha(V)beta(5) integrins and promotes cell motility. Cancer Res 62(18):5358-5364. 2002.

Godovac-Zimmermann, J.; Brown, L. R. Perspectives for mass spectrometry and functional proteomics. Mass Spectrom Rev 20(1)1-57. 2001.

Granville, C. A.; Dennis, P. A. An overview of lung cancer genomics and proteomics. Am J Respir Cell Mol Biol 32(3):169-176. 2005.
Gunawardana, C. G.; Kuk, C.; Smith, C. R.; Batruch, I.; Soosaipillai, A.; Diamandis, E. P. Comprehensive analysis of conditioned media from ovarian cancer cell lines identifies novel candidate markers of epithelial ovarian cancer. J Proteome Res 8(10):4705-4713. 2009.

Gygi, S. P.; Aebersold, R. Mass spectrometry and proteomics. Curr Opin Chem Biol 4(5):489-494. 2000.

Han, C. L.; Chen, J. S.; Chan, E. C.; Wu, C. P.; Yu, K. H.; Chen, K. T.; Tsou, C. C.; Tsai, C. F.; Chien, C. W.; Kuo, Y. B.; Lin, P. Y.; Yu, J. S.; Hsueh, C.; Chen, M. C.; Chan, C. C.; Chang, Y. S.; Chen, Y. J. An informatics-assisted label-free approach for personalized tissue membrane proteomics: case study on colorectal cancer. Mol Cell Proteomics 10:M110.003087. 2011.

Han, C. L.; Chien, C. W.; Chen, W. C.; Chen, Y. R.; Wu, C. P.; Li, H.; Chen, Y. J. A multiplexed quantitative strategy for membrane proteomics: opportunities for mining therapeutic targets for autosomal dominant polycystic kidney disease. Mol Cell Proteomics. 7(10):1983-1997. 2008.

Han, H. J.; Russo, J.; Kohwi, Y.; Kohwi-Shigematsu, T. SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature 452(7184): 187-193. 2008.

Hanahan, D.;Weinberg, R. A. The hallmarks of cancer. Cell 100:57-70 (2000)
Hegele, A.; Heidenreich, A.; Kropf, J.; von Knobloch, R.; Varga, Z.; Hofmann, R.; Olbert, P. Plasma levels of cellular fibronectin in patients with localized and metastatic renal cell carcinoma. Tumour Biol 25(3):111-116. 2004.

Hegele, A.; Hofmann, R.; Kosche, B.; Kropf, J. Evaluation of cellular fibronectin plasma levels as a useful staging tool in different stages of transitional cell carcinoma of the bladder and renal cell carcinoma. Biomark Insights 2:1-7. 2007.

Higgs, R. E.; Knierman, M. D.; Gelfanova, V.; Butler, J. P.; Hale, J. E. Quantitative Analysis of Membrane Proteins from Breast Cancer Cell Lines BT474 and MCF7 Using Multistep Solid Phase Mass Tagging and 2D LC/MS. J Proteome Res 4:1442-1450. 2005.

Holm, S. A simple sequentially rejective multiple test procedure. Scand. J. Statist. 6, 65–70, 1979.

Huang, C.; Rajfur, Z.; Yousefi, N.; Chen, Z.; Jacobson, K.; Ginsberg, M. H. Talin phosphorylation by Cdk5 regulates Smurf1-mediated talin head ubiquitylation and cell migration. Nat Cell Biol 11(5):624-630. 2009.

Huang, L. J.; Chen, S. X.; Huang, Y.; Luo, W. J.; Jiang, H. H.; Hu, Q. H.; Zhang, P. F.; Yi, H. Proteomics-based identification of secreted protein dihydrodiol dehydrogenase as a novel serum markers of non-small cell lung cancer. Lung Cancer 54(1):87-94. 2006.

Huang, L.; Cheng, H. C.; Isom, R.; Chen, C. S.; Levine, R. A.; Pauli, B. U. Protein kinase Cepsilon mediates polymeric fibronectin assembly on the surface of blood-borne rat breast cancer cells to promote pulmonary metastasis. J Biol Chem. 283(12):7616-27. 2008.

Huang, Y.; Prasad, M.; Lemon, W. J.; Hampel, H.; Wright, F. A.; Kornacker, K.; LiVolsi, V.; Frankel, W.; Kloos, R. T.; Eng, C.; Pellegata, N. S.; de la Chapelle, A. Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc Natl Acad Sci USA 98(26):15044-150049. 2001.

Hung, T. T.; Wu, J. Y.; Liu, J. F.; Cheng, H. C. Epitope analysis of the rat dipeptidyl peptidase IV monoclonal antibody 6A3 that blocks pericellular fibronectin-mediated cancer cell adhesion. FEBS J 276(22):6548-6559. 2009.

Hunter, K. W.; Crawford, N. P.; Alsarraj, J. Mechanisms of metastasis. Breast Cancer Research 10:Suppl 1-S2. 2008.

Hynes, R. Molecular biology of fibronectin. Annu Rev Cell Biol 1:67-90. 1985.

Igisu, K. The role of fibronectin in the process of wound healing. Thromb Res 44(4):455-465. 1986.

Ikenaka, Y.; Yoshiji, H.; Kuriyama, S.; Yoshii, J.; Noguchi, R.; Tsujinoue, H.; Yanase, K.; Namisaki, T.; Imazu, H.; Masaki, T.; and Fukui, H. Tissue inhibitor of metalloproteinases-1 (TIMP-1) inhibits tumor growth and angiogenesis in the TIMP-1 transgenic mouse model. Int J Cancer 105(3):340-346. 2003.

Inagaki, D.; Oshima, T.; Yoshihara, K.; Tamura, S.; Kanazawa, A.; Yamada, T.; Yamamoto, N.; Sato, T.; Shiozawa, M.; Morinaga, S.; Akaike, M.; Fujii, S.; Numata, K.; Kunisaki, C.; Rino, Y.; Tanaka, K.; Masuda, M.; Imada, T. Overexpression of tissue inhibitor of metalloproteinase-1 gene correlates with poor outcomes in colorectal cancer. Anticancer Res 30(10):4127-4130. 2010.

Ivaska, J.; Nissinen, L.; Immonen, N.; Eriksson, J. E.; Kähäri, V. M.; Heino, J. Integrin alpha 2 beta 1 promotes activation of protein phosphatase 2A and dephosphorylation of Akt and glycogen synthase kinase 3 beta. Mol Cell Biol 22(5):1352-1359. 2002.
Jacobs, J. M.; Waters, K. M.; Kathmann, L. E.; Camp, D. G.; Wiley, H. S.; Smith, R. D. Thrall BD: The mammary epithelial cell secretome and its regulation by signal transduction pathways. J Proteome Res 7(2):558-569. 2008.

Jacobs, J. M.; Waters, K. M.; Kathmann, L. E.; Camp, D. G.; Wiley, H. S.; Smith, R. D. Thrall BD: The mammary epithelial cell secretome and its regulation by signal transduction pathways. J Proteome Res 7(2):558-569. 2008.

Jee, B. K.; Park, K. M.; Surendran, S.; Lee, W. K.; Han, C. W.; Kim, Y. S.; Lim, Y. KAI1/CD82 suppresses tumor invasion by MMP9 inactivation via TIMP1 up-regulation in the H1299 human lung carcinoma cell line. Biochem Biophys Res Commun 342(2):655-661. 2006.

Jin, L.; Zhang, Y.; Li, H.; Yao, L.; Fu, D.; Yao, X.; Xu, L. X.; Hu, X.; Hu, G. Differential secretome analysis reveals CST6 as a suppressor of breast cancer bone metastasis. Cell Res 22(9):1356-1373.2012.

Kallakury, B. V.; Karikehalli, S.; Haholu, A.; Sheehan, C. E.; Azumi, N.; Ross, J.S. Increased expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinases 1 and 2 correlate with poor prognostic variables in renal cell carcinoma. Clin Cancer Res 7(10):3113-3119. 2001.

Kao, Y. R.; Shih, J. Y.; Wen, W. C.; Ko, Y. P.; Chen, B. M.; Chan, Y. L.; Chu, Y. W.; Yang, P. C.; Wu, C. W.; Roffler, S. R. Tumor-associated antigen L6 and the invasion of human lung cancer cells. Clin Cancer Res 9:2807-2816. 2003.

Karagiannis, G. S.; Petraki, C.; Prassas, I.; Saraon, P.; Musrap, N.; Dimitromanolakis, A.; Diamandis, E. P. Proteomic signatures of the desmoplastic invasion front reveal collagen type XII as a marker of myofibroblastic differentiation during colorectal cancer metastasis. Oncotarget 3(3): 267-285. 2012.

Kawamata, H.; Kawai, K.; Kameyama, S.; Johnson, M. D.; Stetler-Stevenson, W. G.; Oyasu, R. Over-expression of tissue inhibitor of matrix metalloproteinases (TIMP1 and TIMP2) suppresses extravasation of pulmonary metastasis of a rat bladder carcinoma. Int J Cancer 63(5):680-687. 1995.

Koivunen, J., Aaltonen, V., and Peltonen, J. Protein kinase C (PKC) family in cancer progression. Cancer Lett 235:1-10. 2006.

Kopitz, C.; Gerg, M.; Bandapalli, O. R.; Ister, D.; Pennington, C. J.; Hauser, S.; Flechsig, C.; Krell, H. W.; Antolovic, D.; Brew, K.; Nagase, H.; Stangl, M.; von Weyhern, C. W.; Brücher, B. L.; Brand, K.; Coussens, L. M.; Edwards, D. R.; Krüger, A. Tissue inhibitor of metalloproteinases-1 promotes liver metastasis by induction of hepatocyte growth factor signaling. Cancer Res 67(18):8615-8623. 2007.

Kulasingam, V.; Diamandis, E. P. Proteomics analysis of conditioned media from three breast cancer cell lines: a mine for biomarkers and therapeutic targets. Mol Cell Proteomics 6(11):1997-2011. 2007.

Kuo, J. C.; Wang, W. J.; Yao, C. C.; Wu, P. R.; Chen, R. H. The tumor suppressor DAPK inhibits cell motility by blocking the integrin-mediated polarity pathway. J Cell Biol 172:619-631. 2006.

Lawlor, K.; Nazarian, A.; Lacomis, L.; Tempst, P.; Villanueva, J. Pathway-based biomarker search by high-throughput proteomics profiling of secretomes. J Proteome Res 8(3):1489-1503. 2009.

Leber, M. F.; Efferth, T. Molecular principles of cancer invasion and metastasis (review). Int J Oncol 34(4): 881-895. 2009.

Lee, K. H. Proteomics: a technology-driven and technology-limited discovery science. Trends Biotechnol 19(6):217-222. 2001.

Lee, M.; Fridman, R.; Mobashery, S. Extracellular proteases as targets for treatment of cancer metastases. Chem Soc Rev 33:401-409. 2004.

Lee, Y. S.; Chen, P. W.; Tsai, P. J.; Su, S. H.; Liao, P. C. Proteomics analysis revealed changes in rat bronchoalveolar lavage fluid proteins associated with oil mist exposure. Proteomics 6(7):2236-2250. 2006.

Lewis, T. S.; Hunt, J. B.; Aveline, L. D.; Jonscher, K. R.; Louie, D. F.; Yeh, J. M.; Nahreini, T. S.; Resing, K. A.; Ahn, N. G. Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry. Mol Cell 6(6):1343-1354. 2000.

Li, H.; DeSouza, L. V.; Ghanny, S.; Li, W.; Romaschin, A. D.; Colgan, T. J.; Siu, K. W. Identification of candidate biomarker proteins released by human endometrial and cervical cancer cells using two-dimensional liquid chromatography/tandem mass spectrometry. J Proteome Res 6(7):2615-2622. 2007.

Liotta, L. A.; Kohn, E. C. The microenvironment of the tumour-host interface. Nature 411(6835):375-379. 2001.

Liu, H.; Sadygov, R. G.; Yates, J. R. 3rd A model for random sampling and estimation of relative protein abundance in shotgun proteomics. Anal Chem 76:4193-4201. 2004.

Liu, X. W.; Bernardo, M. M.; Fridman, R.; Kim, H. R. Tissue inhibitor of metalloproteinase-1 protects human breast epithelial cells against intrinsic apoptotic cell death via the focal adhesion kinase/phosphatidylinositol 3-kinase and MAPK signaling pathway. J Biol Chem 278(41):40364-40372. 2003.

Lu, X.; Zhu, H. Tube-gel digestion: a novel proteomic approach for high throughput analysis of membrane proteins. Mol Cell Proteomics. 4(12):1948-1958. 2005.

Lu, Y. T.; Han, C. L.; Wu, C. L.; Yu, T. M.; Chien, C. W.; Liu, C. L.; Chen, Y. J. Proteomic profiles of bronchoalveolar lavage fluid from patients with ventilator-associated pneumonia by gel-assisted digestion and 2-D-LC/MS/MS. Proteomics Clin Appl 2(9):1208-1222. 2008.

Mahner, S.; Woelber, L.; Eulenburg, C.; Schwarz, J.; Carney, W.; Jaenicke, F.; Milde-Langosch, K.; Mueller, V. TIMP-1 and VEGF-165 serum concentration during first-line therapy of ovarian cancer patients. BMC Cancer 10:139. 2010.

Mancini, M.; Toker, A. NFAT proteins: emerging roles in cancer progression. Nat Rev Cancer 9:810-820. 2009.

Martin, D. B.; Gifford, D. R.; Wright, M. E.; Keller, A.; Yi, E.; Goodlett, D. R.; Aebersold, R.; Nelson, P. S. Quantitative proteomic analysis of proteins released by neoplastic prostate epithelium. Cancer Res 64(1):347-355. 2004.

Mathivanan, S.; Ji, H.; Simpson, R. J. Exosomes: extracellular organelles important in intercellular communication. J Proteomics 73:1907-1920. 2010.

Mathivanan, S.; Simpson, R. J. ExoCarta: A compendium of exosomal proteins and RNA. Proteomics 9:4997-5000. 2009.

Mbeunkui, F.; Fodstad, O.; Pannell, L. K. Secretory protein enrichment and analysis: an optimized approach applied on cancer cell lines using 2D LC-MS/MS. J Proteome Res 5(4):899-906. 2006.

Mbeunkui, F.; Metge, B. J.; Shevde, L. A.; Pannell, L. K. Identification of differentially secreted biomarkers using LC-MS/MS in isogenic cell lines representing a progression of breast cancer. J Proteome Res 6(8):2993-3002. 2007.

Mehrotra, S.; Languino, L. R.; Raskett, C. M.; Mercurio, A. M.; Dohi, T.; Altieri, D.C. IAP regulation of metastasis. Cancer Cell 17(1):53-64. 2010.

Moller, S.; Croning, M. D.; Apweiler, R. Evaluation of methods for the prediction of membrane spanning regions. Bioinformatics 17:646-653. 2001.

Morgan, K.; Marsters, P.; Morley, S.; van Gent, D.; Hejazi, A.; Backx, M.; Thorpe, E. R.; Kalsheker, N. Oncostatin M induced alpha1-antitrypsin (AAT) gene expression in Hep G2 cells is mediated by a 3' enhancer. Biochem J 365(Pt 2):555-560. 2002.

Mor-Vaknin, N.; Punturieri, A.; Sitwala, K.; Markovitz, D. M. Vimentin is secreted by activated macrophages. Nat Cell Biol 5:59-63. 2003.

Muthusamy, B.; Hanumanthu, G.; Reshmi, R.; Sriranjini, S.; Suresh, S.; Rekha, B.; Srinivas, D.; Karthick, L.; Vrushabendra, B. M.; Sharma, S.; Mishra, G.; Rashmi, B. P.; Kadekar, S.; Chatterjee, P.; Mangala, K. S.; Shivashankar, H. N.; Chandrika, K. N.; Deshpande, N.; Suresh, M.; Kannabiran, N.; Niranjan, V.; Nalli, A.; Prasad, T. S. K.; Arun, K. S.; Reddy, R.; Chandran, S.; Jadhav, T.; Julie, D.; Mahesh, M.; John, S. L.; Palvankar, K.; Sudhir, D.; Bala, P.; Jithesh, M. K.; Rashmi, N. S.; Vishnupriya, G.; Dhar, K.; Reshma, S.; Chaerkady, R.; Prasad, C. K.; Gandhi, T. K. B.; Harsha, H. C.; Mohan, S. S.; Deshpande, K. S.; Sarker, M.; Pandey, A. Plasma proteome database as a resource for proteomics research. Proteomics 5:3531-3536. 2005.

Nguyen, D. X.; Bos, P. D.; Massagué, J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 9:274-284. 2009.

Nickel, W. The mystery of nonclassical protein secretion. A current view on cargo proteins and potential export routes. Eur J Biochem 270:2109-2119. 2003.

Normandin, K.; Péant, B.; Le Page, C.; de Ladurantaye, M.; Ouellet, V.; Tonin, P. N.; Provencher, D. M.; Mes-Masson, A. M. Protease inhibitor SERPINA1 expression in epithelial ovarian cancer. Clin Exp Metastasis 27(1):55-69. 2010.

Pandey, A.; Mann, M. Proteomics to study genes and genomes. Nature 405(6788):837-846. 2000.

Papetti, M.; Herman, I. M. Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol 282(5):C947-70. 2002.

Park, J. E.; Tan, H. S.; Datta, A.; Lai, R. C.; Zhang, H.; Meng, W.; Lim, S. K.; Sze, S. K. Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol Cell Proteomics 9(6): 1085-1099. 2010.

Pesta, M.; Kulda, V.; Kucera, R.; Pesek, M.; Vrzalova, J.; Liska, V.; Pecen, L.; Treska, V.; Safranek, J.; Prazakova, M.; Vycital, O.; Bruha, J.; Holubec, L.; Topolcan, O. Prognostic significance of TIMP-1 in non-small cell lung cancer. Anticancer Res. 31(11), 4031-4038. 2011.

Piersma, S. R.; Fiedler, U.; Span, S.; Lingnau, A.; Pham, T. V.; Hoffmann, S.; Kubbutat, M. H.; Jiménez, C. R. Workflow comparison for label-free, quantitative secretome proteomics for cancer biomarker discovery: method evaluation, differential analysis, and verification in serum. J Proteome Res 9(4):1913-1922. 2010.

Qiu, Q.; Yang, M.; Tsang, B. K.; Gruslin, A. EGF-induced trophoblast secretion of MMP-9 and TIMP-1 involves activation of both PI3K and MAPK signalling pathways. Reproduction 128(3):355-363. 2004.

Quigley, J. P.; Sullivan, L. M.; DeMarinis, C. M.; Gordon, J. R. Functional role of specific secreted and cell surface molecules in tumor cell invasion and metastasis. Ciba Found Symp 141(1):22-47. 1998.

Recchia, I.; Rucci, N.; Festuccia, C.; Bologna, M.; MacKay, A. R.; Migliaccio, S.; Longo, M.; Susa, M.; Fabbro, D.; Teti, A. Pyrrolopyrimidine c-Src inhibitors reduce growth, adhesion, motility and invasion of prostate cancer cells in vitro. Eur J Cancer 39(13), 1927-1935. 2003.

Reed, M. J.; Koike, T.; Sadoun, E.; Sage, E. H.; Puolakkainen, P. Inhibition of TIMP1 enhances angiogenesis in vivo and cell migration in vitro. Microvasc Res 65(1):9-17. 2003.

Reuter, J. A.; Ortiz-Urda, S.; Kretz, M.; Garcia, J.; Scholl, F. A.; Pasmooij, A. M.; Cassarino, D.; Chang, H. Y.; Khavari, P. A. Modeling inducible human tissue neoplasia identifies an extracellular matrix interaction network involved in cancer progression. Cancer Cell 15(6):477-488. 2009.

Rudnick, D. A.; Shikapwashya, O.; Blomenkamp, K.; Teckman, J. H. Indomethacin increases liver damage in a murine model of liver injury from alpha-1-antitrypsin deficiency. Hepatology 44(4):976-982. 2006.

Rybak, J. N.; Roesli, C.; Kaspar, M.; Villa, A.; Neri, D. The extra-domain A of fibronectin is a vascular marker of solid tumors and metastases. Cancer Res 67(22):10948-10957. 2007.

Samani, A. A.; Yakar, S.; LeRoith, D.; Brodt, P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev 28:20-47. 2007.

Sarkar, F. H.; Li, Y.; Wang, Z.; Kong, D. Pancreatic cancer stem cells and EMT in drug resistance and metastasis. Minerva Chir 64(5):489-500. 2009.

Scamuffa, N.; Siegfried, G.; Bontemps, Y.; Ma, L.; Basak, A.; Cherel, G.; Calvo, F.; Seidah, N. G.; Khatib, A. M. Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells. J Clin Invest 118(1):352-363. 2008.

Schelter, F.; Halbgewachs, B.; Bäumler, P.; Neu, C.; Görlach, A.; Schrötzlmair, F.; Krüger, A. Tissue inhibitor of metalloproteinases-1-induced scattered liver metastasis is mediated by hypoxia-inducible factor-1α. Clin Exp Metastasis 28(2):91-99. 2011.

Schiller, J. H.; Harrington, D.; Belani, C. P.; Langer, C.; Sandler, A.; Krook, J.; Zhu, J.; Johnson, D. H. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Engl J Med 346(2):92-98. 2002.

Shen, W.; Zhu, J.; Yu, Z.; Xue, Q. TIMP-1 secreted by fibroblasts inhibits tumor cell invasion and metastasis in mouse melanoma. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 26(3):610-614. 2009.

Shi, C. S.; Kehrl, J. H. Pyk2 amplifies epidermal growth factor and c-Src-induced Stat3 activation. J Biol Chem 279(17):17224-17231. 2004.

Shi, Y.; Parhar, R. S.; Zou, M.; Al-Mohanna, F. A.; Paterson, M. C. Gene therapy of melanoma pulmonary metastasis by intramuscular injection of plasmid DNA encoding tissue inhibitor of metalloproteinases-1. Cancer Gene Ther 9(2):126-132. 2002.

Shih, J. Y.; Yang, S. C.; Hong, T. M.; Yuan, A.; Chen, J. J.; Yu, C. J.; Chang, Y. L.; Lee, Y. C.; Peck, K.; Wu, C. W.; Yang, P. C. Collapsin response mediator protein-1 and the invasion and metastasis of cancer cells. J Natl Cancer Inst 93:1392-1400. 2001.

Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2012. CA Cancer J Clin 62(1):10-29. 2012.

Siesser, P. M.; Meenderink, L. M.; Ryzhova, L.; Michael, K. E.; Dumbauld, D. W.; García, A. J.; Kaverina, I.; Hanks, S. K. A FAK/Src chimera with gain-of-function properties promotes formation of large peripheral adhesions associated with dynamic actin assembly. Cell Motil Cytoskeleton 65(1):25-39. 2008.

Simi, L.; Andreani, M.; Davini, F.; Janni, A.; Pazzagli, M.; Serio, M.; Orlando, C. Simultaneous measurement of MMP9 and TIMP1 mRNA in human non small cell lung cancers by multiplex real time RT-PCR. Lung Cancer. 45(2), 171-179. 2004.

Singh, P.; Carraher, C.; Schwarzbauer, J. E. Assembly of fibronectin extracellular matrix. Annu Rev Cell Dev Biol 26:397-419. 2010.

Sung, H. J.; Cho, J. Y. Biomarkers for the lung cancer diagnosis and their advances in proteomics. BMB Rep 41:615-625. 2008.

Suzuki, M.; Oda, E.; Nakajima, T.; Sekiya, S.; Oda, K. Induction of Sp1 in differentiating human embryonal carcinoma cells triggers transcription of the fibronectin gene. Mol Cell Biol 18(5):3010-3020. 1998.

Tarin, D.; Price, J. E. Influence of microenvironment and vascular anatomy on "metastatic" colonization potential of mammary tumors. Cancer Res 41(9 Pt 1):3604-3609. 1981.

Taro, Hayakawa. Multiple functions of tissue inhibitors of metalloproteinases (TIMPs): a new aspect involving osteoclastic bone resorption. J Bone Miner Metab. 20, 1–13. 2002.

Taube, M. E.; Liu, X. W.; Fridman, R.; Kim, H. R. TIMP-1 regulation of cell cycle in human breast epithelial cells via stabilization of p27(KIP1) protein. Oncogene 25(21):3041-3048. 2006.

Taylor, A. M.; Holst, O.; Thomas-Oates, J. Mass spectrometric profiling of O-linked glycans released directly from glycoproteins in gels using in-gel reductive beta-elimination. Proteomics. 6(10):2936-2946. 2006.

Thant, A. A.; Nawa, A.; Kikkawa, F.; Ichigotani, Y.; Zhang, Y.; Sein, T. T.; Amin, A. R.; Hamaguchi, M. Fibronectin activates matrix metalloproteinase-9 secretion via the MEK1-MAPK and the PI3K-Akt pathways in ovarian cancer cells. Clin Exp Metastasis 18(5): 423-428. 2000.

Théry, C.; Ostrowski, M.; Segura, E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9:581-593. 2009.

Thomas, N. P.; Søren, B.; Gunnar, V. H.; Henrik, N. SignalP 4.0: discriminating signal peptides from transmembrane regions. Nature Methods 8:785-786. 2011.

Thompson, E. W.; Williams, E. D. EMT and MET in carcinoma--clinical observations, regulatory pathways and new models. Clin Exp Metastasis 25:591-592. 2008.

Tjalsma, H.; Bolhuis, A.; Jongbloed, J. D.; Bron, S.; van Dijl, J. M. Signal peptide-dependent protein transport in Bacillus subtilis: a genome-based survey of the secretome. Microbiol Mol Biol Rev 64(3):515-547. 2000.

Valkova, C.; Maerz, S.; Imhof, D.; Liebmann, C. Protein kinase Cepsilon may act as EGF-inducible scaffold protein for phospholipase Cgamma1. Cell Signal 19(9):1830-1843. 2007.

Volmer, M. W.; Stuhler, K.; Zapatka, M.; Schoneck, A.; Klein-Scory, S.; Schmiegel, W.; Meyer, H. E.; Schwarte-Waldhoff, I. Differential proteome analysis of conditioned media to detect Smad4 regulated secreted biomarkers in colon cancer. Proteomics 5(10):2587-2601. 2005.

Wajapeyee, N.; Serra, R. W.; Zhu, X.; Mahalingam, M.; Green, M. R. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 132:363-374. 2008.

Wang, C. C.; Tsai, M. F.; Hong, T. M.; Chang, G. C.; Chen, C. Y.; Yang, W. M.; Chen, J. J.; Yang, P. C. The transcriptional factor YY1 upregulates the novel invasion suppressor HLJ1 expression and inhibits cancer cell invasion. Oncogene 24:4081-4093. 2005.

Wang, C. L.; Wang, C. I.; Liao, P. C.; Chen, C. D.; Liang, Y.; Chuang, W. Y.; Tsai, Y. H.; Chen, H. C.; Chang, Y. S.; Yu, J. S.; Wu, C. C.; Yu, C. J. Discovery of retinoblastoma-associated binding protein 46 as a novel prognostic marker for distant metastasis in nonsmall cell lung cancer by combined analysis of cancer cell secretome and pleural effusion proteome. J Proteome Res 8(10):4428-4440. 2009.

Wang, C. S.; Wu, T. L.; Tsao, K. C.; Sun, C. F. Serum TIMP-1 in gastric cancer patients: a potential prognostic biomarker. Ann Clin Lab Sci 36(1):23-30. 2006.

Wang, G.; Wu, W. W.; Zeng, W.; Chou, C. L.; Shen, R. F. Label-Free Protein Quantification Using LC-Coupled Ion Trap or FT Mass Spectrometry:  Reproducibility, Linearity, and Application with Complex Proteomes. J Proteome Res 5:1214-1223. 2006.

Wang, W.; Zhou, H.; Lin, H.; Roy, S.; Shaler, T. A.; Hill, L. R.; Norton, S.; Kumar, P.; Anderle, M.; Becker, C. H. Quantification of Proteins and Metabolites by Mass Spectrometry without Isotopic Labeling or Spiked Standards. Anal Chem 75:4818-4826. 2003.

Wang, X.Y.; Wang, Y.; Liu, H.C. Tamoxifen lowers the MMP-9/TIMP-1 ratio and inhibits the invasion capacity of ER-positive non-small cell lung cancer cells. Biomed Pharmacother. 65(7):525-528. 2011.

Washburn, M. P.; Wolters, D.; Yates, J. R. 3rd Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol 19:242-247. 2001.

Wiener, M. C.; Sachs, J. R.; Deyanova, E. G.; Yates, N. A. Differential Mass Spectrometry:  A Label-Free LC−MS Method for Finding Significant Differences in Complex Peptide and Protein MixturesAnal. Chem 76:6085-6096. 2004.

Wong, F. H.; Huang, C. Y.; Su, L. J.; Wu, Y. C.; Lin, Y. S.; Hsia, J. Y.; Tsai, H. T.; Lee, S. A.; Lin, C. H.; Tzeng, C. H.; Chen, P. M.; Chen, Y. J.; Liang, S. C.; Lai, J. M.; Yen, C. C. Combination of microarray profiling and protein-protein interaction databases delineates the minimal discriminators as a metastasis network for esophageal squamous cell carcinoma. Int J Oncol 34(1):117-128. 2009.

Wong, S. Y.; Hynes, R. O. Lymphatic or hematogenous dissemination: how does a metastatic tumor cell decide? Cell Cycle 5:812-817. 2006

Woźniak, B.; Mila-Kierzenkowska, C.; Woźniak, A.; Drewa, G.; Sopońska, M.; Drewa, T.; Krzyzyńska-Malinowska, E.; Makarewicz, R.; Kowalski, T.; Szmytkowska, K. The effect of combined therapy on activity of cathepsin D and alpha-1-antitrypsin in the blood serum of women with cervical cancer. Eur J Gynaecol Oncol 29(6):617-619. 2008.

Wu, C. C.; Hsu, C. W.; Chen, C. D.; Yu, C. J.; Chang, K. P.; Tai, D. I.; Liu, H. P.; Su, W. H.; Chang, Y. S.; Yu, J. S. Candidate serological biomarkers for cancer identified from the secretomes of 23 cancer cell lines and the human protein atlas. Mol Cell Proteomics. 9(6):1100-1117. 2010.

Würtz, S. Ø.; Schrohl, A. S.; Sørensen, N. M.; Lademann, U.; Christensen, I. J.; Mouridsen, H.; Brünner, N. Tissue inhibitor of metalloproteinases-1 in breast cancer. Endocr Relat Cancer 12(2):215-227. 2005

Xiao, T.; Ying, W.; Li, L.; Hu, Z.; Ma, Y.; Jiao, L.; Ma, J.; Cai, Y.; Lin, D.; Guo, S.; Han, N.; Di, X.; Li, M.; Zhang, D.; Su, K.; Yuan, J.; Zheng, H.; Gao, M.; He, J.; Shi, S.; Li, W.; Xu, N.; Zhang, H.; Liu, Y.; Zhang, K.; Gao, Y.; Qian, X.; Cheng, S. An approach to studying lung cancer-related proteins in human blood. Mol Cell Proteomics 4(10):1480-1486. 2005.

Xue, H.; Lu, B.; Lai, M. The cancer secretome: a reservoir of biomarkers. J Transl Med 6(1):52. 2008.

Xue, H.; Lü, B.; Zhang, J.; Wu, M.; Huang, Q.; Wu, Q.; Sheng, H.; Wu, D.; Hu, J.; Lai, M. Identification of serum biomarkers for colorectal cancer metastasis using a differential secretome approach. J Proteome Res 9(1): 545-555. 2010.

Yamauchi, K.; Ogata, Y.; Nagase, H.; Shirouzu, K. Inhibition of liver metastasis from orthotopically implanted colon cancer in nude mice by transfection of the TIMP-1 gene into KM12SM cells. Surg Today 31(9):791-798. 2001.

Yan, W.; Chen, S. S. Mass spectrometry-based quantitative proteomic profiling. Brief Funct Genomic Proteomic 4(1):27-38. 2005.

Yang, J. C.; Haworth, L.; Sherry, R. M.; Hwu, P.; Schwartzentruber, D. J.; Topalian, S. L.; Steinberg, S. M.; Chen, H. X.; Rosenberg, S. A. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349(5): 427-434. 2003.

Yang, J.; Weinberg, R. A. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 14:818-829. 2008.

Yang, M. H.; Wu, K. J. TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development. Cell Cycle 7:2090-2096. 2008.

Yang, P. C.; Luh, K. T.; Wu, R.; Wu, C. W. Characterization of the mucin differentiation in human lung adenocarcinoma cell lines. Am J Respir Cell Mol Biol 7:161-171. 1992.

Yang, Y.; Lim, S. K.; Choong, L. Y.; Lee, H.; Chen, Y.; Chong, P. K.; Ashktorab, H.; Wang, T. T.; Salto-Tellez, M.; Yeoh, K. G.; Lim, Y. P. Cathepsin S mediates gastric cancer cell migration and invasion via a putative network of metastasis-associated proteins. J Proteome Res 9(9): 4767-4778. 2010.

Yate, J. R. 3rd. Mass Spectrometry: From genomics to proteomics. Trends Genet 16(1):5-8. 2000.

Ylätupa, S.; Haglund, C.; Mertaniemi, P.; Vahtera, E.; Partanen, P. Cellular fibronectin in serum and plasma: a potential new tumour marker? Br J Cancer 71(3):578-582. 1995.

Zeidman, I. Metastasis: a review of recent advances. Cancer Res 17(3):157-162. 1957.

Zelvyte, I.; Wallmark, A.; Piitulainen, E.; Westin, U.; Janciauskiene, S. Increased plasma levels of serine proteinase inhibitors in lung cancer patients. Anticancer Res 24(1):241-247. 2004.
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