進階搜尋


下載電子全文  
系統識別號 U0026-1905201515463200
論文名稱(中文) 探討cAMP次級傳遞因子對於PMA刺激人類血癌細胞株HEL細胞轉移之影響
論文名稱(英文) The effect of cAMP on PMA-stimulated cell migration in HEL cells
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 103
學期 2
出版年 104
研究生(中文) 張瑋珊
研究生(英文) Wei-Shan Chang
學號 S26011033
學位類別 碩士
語文別 中文
論文頁數 73頁
口試委員 指導教授-簡偉明
口試委員-陳清玉
口試委員-錢偉鈞
中文關鍵字 環腺苷單磷酸  急性骨髓性白血病  轉移  基質金屬蛋白酶  佛波脂 
英文關鍵字 cAMP  AML  metastasis  matrix metalloproteinase-9 (MMP-9)  PMA 
學科別分類
中文摘要 部分的急性骨髓性白血病(AML)可使用全反式維甲酸誘導細胞分化,並合併化學治療,但有文獻指出全反式維甲酸治療可能導致血癌轉移和骨髓復發,將會影響病人的預後。血癌最常見也最嚴重的轉移位置是軟腦膜轉移,存活率只有2到6個月。已知過去研究血癌細胞轉移的機制,不同的細胞內環腺苷單磷酸(cAMP)濃度會影響纖維母細胞、角質細胞以及嗜中性顆粒球的細胞移動能力,但其影響隨不同細胞型態而異。本實驗室以佛波脂(PMA)誘導人類血癌細胞株 HEL分化,發現HEL受PMA刺激之下,細胞型態會產生異質化的情況,而在forskolin前處理的情況下,接受PMA刺激後,雙極細胞的比例與細胞的移動速率皆有明顯的增加。並且使用明膠蛋白酵素電泳法和西方墨點法,發現在PMA刺激之下,HEL細胞釋放基質金屬蛋白酶 (MMP-9),並具酵素活性;而在前處理forskolin的HEL細胞,經由PMA刺激後,MMP-9的活性和蛋白量有明顯增加,顯示HEL細胞侵噬能力增加。因此本研究以此細胞模型進一步探討cAMP 促進HEL細胞分泌的MMP-9 蛋白量和酵素活性的詳細機制。實驗結果發現分別使用新穎型PKCs (PKCδ、PKCε)、p38和ERK1/2的抑制劑,會減少MMP-9蛋白質含量和酵素活性;進一步使用目標基因靜默與細胞轉染,確認PKCδ參與在其中。從以上的實驗結果我們歸納出cAMP促進PMA刺激的HEL細胞遷移與侵襲現象,有一部分是透過增加MMP-9蛋白質含量和酵素活性,並且是透過兩個層面:(1)促進 PKCδ的活性,(2) MAPKs中的p38和ERK1/2訊息傳遞,進而影響HEL細胞轉移的現象。
英文摘要 Some types of acute myeloid leukemia (AML) can be treated with all-trans retinoic acid (ATRA), which induces cell differentiation, in combination with other chemotherapeutics. However, previous studies indicated ATRA could lead to leukemia metastasis and bone marrow recurrence, affecting the prognosis. Lepmeningeal metastasis is the most common and severe. With respect to the mechanism of leukemia metastasis, previous reports have shown that the concentration of cAMP in different cells affect fibroblast, keratocyte and neutrophil cell motilities. However, the effects could vary on cell type, and the mechanism in leukemia metastasis is not clear. We induced human erythroleukemia cell (HEL) differentiation by PMA in the absence and presence of intracellular cAMP increasing. The morphology of PMA-stimulated HEL cells turned to be heterogeneous. With forskolin pretreatment, dipolar-shaped cells and cell motilities increased. Moreover, PMA-stimulated HEL cells released matrix metalloproteinase-9 (MMP-9). MMP-9 protein level and activity were examined by Western blot and gelatin zymography respectively. MMP-9 protein level and activity were increased apparently while forskolin-pretreated, suggesting the invasive ability increased. In this report, the mechanism of the regulation of cAMP in the synthesis and secretion of MMP-9 has been investigated. Using the inhibitor experiments, we found novel PKCs, p38 and ERK1/2 were involved. PKCδ was further confirmed by RNA interference. Taken together, cAMP can improve PMA-stimulated HEL cell migration and invasion partly through increasing the expression and activity of MMP-9, and PKCδ, p38 and ERK1/2 were involved.
論文目次 口試合格證明 I
摘要 II
Extended Abstract III
致謝 VI
目錄 VII
圖表目錄 VIII
縮寫表 IX

緒論 1
材料與方法 14
實驗結果 29
討論 35
結論 40
參考文獻 41
附錄 53
參考文獻 Abbott, N.J., Ronnback, L., and Hansson, E. (2006). Astrocyte-endothelial interactions at the blood-brain barrier. Nature reviews Neuroscience 7, 41-53.
Aguayo, A., Giles, F., and Albitar, M. (2003). Vascularity, angiogenesis and angiogenic factors in leukemias and myelodysplastic syndromes. Leukemia & lymphoma 44, 213-222.
Baldassarre, M., Pompeo, A., Beznoussenko, G., Castaldi, C., Cortellino, S., McNiven, M.A., Luini, A., and Buccione, R. (2003). Dynamin participates in focal extracellular matrix degradation by invasive cells. Molecular biology of the cell 14, 1074-1084.
Basset, P., Okada, A., Chenard, M.P., Kannan, R., Stoll, I., Anglard, P., Bellocq, J.P., and Rio, M.C. (1997). Matrix metalloproteinases as stromal effectors of human carcinoma progression: therapeutic implications. Matrix biology : journal of the International Society for Matrix Biology 15, 535-541.
Benekli, M., Savas, M.C., Haznedaroglu, I.C., and Dündar, S.V. (1996). Granulocytic sarcoma in acute promyelocytic leukemia. Leukemia & lymphoma 22, 183-185.
Benekli, M., Savaş, M.C., Haznedaroǧlu, I.C., Dündar, S.V., Weiss, M., and Warrell, R.P. (1995). Two cases of extramedullary acute promyelocytic leukemia. Cancer 76, 151-152.
Bowden, E.T., Barth, M., Thomas, D., Glazer, R.I., and Mueller, S.C. (1999). An invasion-related complex of cortactin, paxillin and PKCmu associates with invadopodia at sites of extracellular matrix degradation. Oncogene 18, 4440-4449.
Buccione, R., Orth, J.D., and McNiven, M.A. (2004). Foot and mouth: podosomes, invadopodia and circular dorsal ruffles. Nature reviews Molecular cell biology 5, 647-657.
Casalou, C., Fragoso, R., Nunes, J.F., and Dias, S. (2007). VEGF/PLGF induces leukemia cell migration via P38/ERK1/2 kinase pathway, resulting in Rho GTPases activation and caveolae formation. Leukemia 21, 1590-1594.
Cavaliere, R., and Schiff, D. (2007). Chemotherapy and cerebral metastases: misperception or reality? Neurosurgical focus 22, E6.
Chakraborti, S., Mandal, M., Das, S., Mandal, A., and Chakraborti, T. (2003). Regulation of matrix metalloproteinases an overview. Molecular and Cellular Biochemistry.
Chen, W.T. (1989). Proteolytic activity of specialized surface protrusions formed at rosette contact sites of transformed cells. The Journal of experimental zoology 251, 167-185.
Cheng, J.C., Chou, C.H., Kuo, M.L., and Hsieh, C.Y. (2006). Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-kappaB signal transduction pathway. Oncogene 25, 7009-7018.
Chien, Y.C., Huang, G.J., Cheng, H.C., Wu, C.H., and Sheu, M.J. (2012). Hispolon attenuates balloon-injured neointimal formation and modulates vascular smooth muscle cell migration via AKT and ERK phosphorylation. Journal of natural products 75, 1524-1533.
Choi, J.H., Choi, K.C., Auersperg, N., and Leung, P.C. (2006). Gonadotropins activate proteolysis and increase invasion through protein kinase A and phosphatidylinositol 3-kinase pathways in human epithelial ovarian cancer cells. Cancer Res 66, 3912-3920.
Christian, F., Szaszak, M., Friedl, S., Drewianka, S., Lorenz, D., Goncalves, A., Furkert, J., Vargas, C., Schmieder, P., Gotz, F., et al. (2011). Small molecule AKAP-protein kinase A (PKA) interaction disruptors that activate PKA interfere with compartmentalized cAMP signaling in cardiac myocytes. The Journal of biological chemistry 286, 9079-9096.
Clemens, M.J., Trayner, I., and Menaya, J. (1992). The role of protein kinase C isoenzymes in the regulation of cell proliferation and differentiation. J Cell Sci 103 ( Pt 4), 881-887.
Curran, S., and Murray, G.I. (2000). Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. European journal of cancer (Oxford, England : 1990) 36, 1621-1630.
Davidson, L.A., and Keller, R.E. (1999). Neural tube closure in Xenopus laevis involves medial migration, directed protrusive activity, cell intercalation and convergent extension. Development (Cambridge, England) 126, 4547-4556.
de Bont, E.S., Rosati, S., Jacobs, S., Kamps, W.A., and Vellenga, E. (2001). Increased bone marrow vascularization in patients with acute myeloid leukaemia: a possible role for vascular endothelial growth factor. British journal of haematology 113, 296-304.
Di Raimondo, F., Palumbo, G.A., Azzaro, M.P., and Giustolisi, R. (2000). Angiogenesis in acute myeloid leukemia. Blood 96, 3656-3659.
Divoli, A., Mendonca, E.A., Evans, J.A., and Rzhetsky, A. (2011). Conflicting biomedical assumptions for mathematical modeling: the case of cancer metastasis. PLoS computational biology 7, e1002132.
Downey, G.P., Chan, C.K., Lea, P., Takai, A., and Grinstein, S. (1992). Phorbol ester-induced actin assembly in neutrophils: role of protein kinase C. The Journal of cell biology 116, 695-706.
Egeblad, M., and Werb, Z. (2002). New functions for the matrix metalloproteinases in cancer progression. Nature Reviews Cancer 2, 161-174.
Eliceiri, B.P., and Cheresh, D.A. (1999). The role of alphav integrins during angiogenesis: insights into potential mechanisms of action and clinical development. The Journal of clinical investigation 103, 1227-1230.
Farina, K.L., Wyckoff, J.B., Rivera, J., Lee, H., Segall, J.E., Condeelis, J.S., and Jones, J.G. (1998). Cell motility of tumor cells visualized in living intact primary tumors using green fluorescent protein. Cancer Res 58, 2528-2532.
Feng, S., Cen, J., Huang, Y., Shen, H., Yao, L., Wang, Y., and Chen, Z. (2011). Matrix metalloproteinase-2 and -9 secreted by leukemic cells increase the permeability of blood-brain barrier by disrupting tight junction proteins. PloS one 6, e20599.
Gausdal, G., Wergeland, A., Skavland, J., Nguyen, E., Pendino, F., Rouhee, N., McCormack, E., Herfindal, L., Kleppe, R., Havemann, U., et al. (2013). Cyclic AMP can promote APL progression and protect myeloid leukemia cells against anthracycline-induced apoptosis. Cell death & disease 4, e516.
Giancotti, F.G., and Ruoslahti, E. (1999). Integrin signaling. Science 285, 1028-1032.
Giannelli, G., Falk-Marzillier, J., Schiraldi, O., Stetler-Stevenson, W.G., and Quaranta, V. (1997). Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5. Science 277, 225-228.
Goel, G., Makkar, H.P., Francis, G., and Becker, K. (2007). Phorbol esters: structure, biological activity, and toxicity in animals. International journal of toxicology 26, 279-288.
Goichberg, P., Kalinkovich, A., Borodovsky, N., Tesio, M., Petit, I., Nagler, A., Hardan, I., and Lapidot, T. (2006). cAMP-induced PKCzeta activation increases functional CXCR4 expression on human CD34+ hematopoietic progenitors. Blood 107, 870-879.
Goicoechea, S., Arneman, D., Disanza, A., Garcia-Mata, R., Scita, G., and Otey, C.A. (2006). Palladin binds to Eps8 and enhances the formation of dorsal ruffles and podosomes in vascular smooth muscle cells. J Cell Sci 119, 3316-3324.
Grabarek, J., Raychowdhury, M., Ravid, K., Kent, K.C., Newman, P., and Ware, J. (1992). Identification and functional characterization of protein kinase C isozymes in platelets and HEL cells. Journal of Biological Chemistry 267, 10011-10017.
Guillemin, M.C., Raffoux, E., Vitoux, D., Kogan, S., Soilihi, H., Lallemand-Breitenbach, V., Zhu, J., Janin, A., Daniel, M.T., Gourmel, B., et al. (2002). In Vivo Activation of cAMP Signaling Induces Growth Arrest and Differentiation in Acute Promyelocytic Leukemia. Journal of Experimental Medicine 196, 1373-1380.
Gum, R., Lengyel, E., Juarez, J., Chen, J.H., Sato, H., Seiki, M., and Boyd, D. (1996). Stimulation of 92-kDa gelatinase B promoter activity by ras is mitogen-activated protein kinase kinase 1-independent and requires multiple transcription factor binding sites including closely spaced PEA3/ets and AP-1 sequences. The Journal of biological chemistry 271, 10672-10680.
Gum, R., Wang, H., Lengyel, E., Juarez, J., and Boyd, D. (1997). Regulation of 92 kDa type IV collagenase expression by the jun aminoterminal kinase- and the extracellular signal-regulated kinase-dependent signaling cascades. Oncogene 14, 1481-1493.
Hagedorn, M., and Bikfalvi, A. (2000). Target molecules for anti-angiogenic therapy: from basic research to clinical trials. Critical reviews in oncology/hematology 34, 89-110.
Hai, C.M., Hahne, P., Harrington, E.O., and Gimona, M. (2002). Conventional protein kinase C mediates phorbol-dibutyrate-induced cytoskeletal remodeling in a7r5 smooth muscle cells. Experimental cell research 280, 64-74.
Hanemaaijer, R., Verheijen, J.H., Maguire, T.M., Visser, H., Toet, K., McDermott, E., O'Higgins, N., and Duffy, M.J. (2000). Increased gelatinase-A and gelatinase-B activities in malignant vs. benign breast tumors. International journal of cancer Journal international du cancer 86, 204-207.
Heidkamp, M.C., Bayer, A.L., Martin, J.L., and Samarel, A.M. (2001). Differential Activation of Mitogen-Activated Protein Kinase Cascades and Apoptosis by Protein Kinase C and in Neonatal Rat Ventricular Myocytes. Circulation Research 89, 882-890.
Herbst, R.S., Yano, S., Kuniyasu, H., Khuri, F.R., Bucana, C.D., Guo, F., Liu, D., Kemp, B., Lee, J.J., Hong, W.K., et al. (2000). Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage I non-small cell lung carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 6, 790-797.
Hwang, Y.P., and Jeong, H.G. (2010). Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase-9 activation through a calcium and protein kinase Calpha-dependent pathway: phorbol-12-myristate-13-acetate-induced/extracellular signal-regulated kinase/activator protein-1. British journal of pharmacology 160, 1195-1211.
Itoh, T., Tanioka, M., Yoshida, H., Yoshioka, T., Nishimoto, H., and Itohara, S. (1998). Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res 58, 1048-1051.
Iwabu, A., Smith, K., Allen, F.D., Lauffenburger, D.A., and Wells, A. (2004). Epidermal growth factor induces fibroblast contractility and motility via a protein kinase C delta-dependent pathway. The Journal of biological chemistry 279, 14551-14560.
Jespersen, C., Doller, A., Akool el, S., Bachmann, M., Muller, R., Gutwein, P., Muhl, H., Pfeilschifter, J., and Eberhardt, W. (2009). Molecular mechanisms of nitric oxide-dependent inhibition of TPA-induced matrix metalloproteinase-9 (MMP-9) in MCF-7 cells. Journal of cellular physiology 219, 276-287.
Johnsen, M., Lund, L.R., Romer, J., Almholt, K., and Dano, K. (1998). Cancer invasion and tissue remodeling: common themes in proteolytic matrix degradation. Current opinion in cell biology 10, 667-671.
Kang, D.W., Park, M.H., Lee, Y.J., Kim, H.S., Kwon, T.K., Park, W.S., and Min do, S. (2008). Phorbol ester up-regulates phospholipase D1 but not phospholipase D2 expression through a PKC/Ras/ERK/NFkappaB-dependent pathway and enhances matrix metalloproteinase-9 secretion in colon cancer cells. The Journal of biological chemistry 283, 4094-4104.
Kiley, S.C., Clark, K.J., Duddy, S.K., Welch, D.R., and Jaken, S. (1999). Increased protein kinase C delta in mammary tumor cells: relationship to transformtion and metastatic progression. Oncogene 18, 6748-6757.
Kim, S., Choi, J.H., Lim, H.I., Lee, S.K., Kim, W.W., Kim, J.S., Kim, J.H., Choe, J.H., Yang, J.H., Nam, S.J., et al. (2009a). Silibinin prevents TPA-induced MMP-9 expression and VEGF secretion by inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells. Phytomedicine : international journal of phytotherapy and phytopharmacology 16, 573-580.
Kim, S., Choi, M.G., Lee, H.S., Lee, S.K., Kim, S.H., Kim, W.W., Hur, S.M., Kim, J.H., Choe, J.H., Nam, S.J., et al. (2009b). Silibinin suppresses TNF-alpha-induced MMP-9 expression in gastric cancer cells through inhibition of the MAPK pathway. Molecules 14, 4300-4311.
Klein, G., Vellenga, E., Fraaije, M.W., Kamps, W.A., and de Bont, E.S. (2004). The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Critical reviews in oncology/hematology 50, 87-100.
Kristensson, K. (2011). Microbes' roadmap to neurons. Nature reviews Neuroscience 12, 345-357.
L, D., P, H., C, M., A, C., R, G., JM, F., A, N., and P., J. (2002). Matrix and serine protease expression during leukemic cell differentiation induced by aclacinomycin and ATRA. Biochem Pharmacol
Langlois, A., Chouinard, F., Flamand, N., Ferland, C., Rola-Pleszczynski, M., and Laviolette, M. (2009). Crucial implication of protein kinase C (PKC)-delta, PKC-zeta, ERK-1/2, and p38 MAPK in migration of human asthmatic eosinophils. J Leukoc Biol 85, 656-663.
Lederman, C.A., Weisberger, J., Seiter, K., and Feldman, E.J. (1995). Differentiation of extramedullary acute promyelocytic leukemia by all-trans-retinoic acid. Leukemia & lymphoma 18, 189-193.
Lee, A.W. (1999). Synergistic activation of mitogen-activated protein kinase by cyclic AMP and myeloid growth factors opposes cyclic AMP's growth-inhibitory effects. Blood 93, 537-553.
Li, C., Wernig, F., Leitges, M., Hu, Y., and Xu, Q. (2003). Mechanical stress-activated PKCdelta regulates smooth muscle cell migration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17, 2106-2108.
Liekens, S., De Clercq, E., and Neyts, J. (2001). Angiogenesis: regulators and clinical applications. Biochemical pharmacology 61, 253-270.
Lin, L.I., Lin, D.T., Chang, C.J., Lee, C.Y., Tang, J.L., and Tien, H.F. (2002). Marrow matrix metalloproteinases (MMPs) and tissue inhibitors of MMP in acute leukaemia: potential role of MMP-9 as a surrogate marker to monitor leukaemic status in patients with acute myelogenous leukaemia. British journal of haematology 117, 835-841.
Linder, S., and Aepfelbacher, M. (2003). Podosomes: adhesion hot-spots of invasive cells. Trends in cell biology 13, 376-385.
Lyden, D., Welch, D.R., and Psaila, B. (2011). Cancer metastasis: biologic basis and therapeutics (Cambridge University Press).
Marquez-Curtis, L.A., Dobrowsky, A., Montano, J., Turner, A.R., Ratajczak, J., Ratajczak, M.Z., and Janowska-Wieczorek, A. (2001). Matrix metalloproteinase and tissue inhibitors of metalloproteinase secretion by haematopoietic and stromal precursors and their production in normal and leukaemic long-term marrow cultures. British journal of haematology 115, 595-604.
Martiny-Baron, G., Kazanietz, M.G., Mischak, H., Blumberg, P.M., Kochs, G., Hug, H., Marme, D., and Schachtele, C. (1993). Selective inhibition of protein kinase C isozymes by the indolocarbazole Go 6976. The Journal of biological chemistry 268, 9194-9197.
Masur, K., Lang, K., Niggemann, B., Zanker, K.S., and Entschladen, F. (2001). High PKC alpha and low E-cadherin expression contribute to high migratory activity of colon carcinoma cells. Molecular biology of the cell 12, 1973-1982.
McDonnell, S.E., Kerr, L.D., and Matrisian, L.M. (1990). Epidermal growth factor stimulation of stromelysin mRNA in rat fibroblasts requires induction of proto-oncogenes c-fos and c-jun and activation of protein kinase C. Molecular and cellular biology 10, 4284-4293.
Minato, N., and Hattori, M. (2009). Spa-1 (Sipa1) and Rap signaling in leukemia and cancer metastasis. Cancer science 100, 17-23.
Moehler, T., Ho, A., Goldschmidt, H., and Barlogie, B. (2003). Angiogenesis in hematologic malignancies. Critical reviews in oncology/hematology 45, 227-244.
Nagase, H., and Woessner, J.F., Jr. (1999). Matrix metalloproteinases. The Journal of biological chemistry 274, 21491-21494.
Nakahara, H., Mueller, S.C., Nomizu, M., Yamada, Y., Yeh, Y., and Chen, W.T. (1998). Activation of beta1 integrin signaling stimulates tyrosine phosphorylation of p190RhoGAP and membrane-protrusive activities at invadopodia. The Journal of biological chemistry 273, 9-12.
Ng, T., Parsons, M., Hughes, W.E., Monypenny, J., Zicha, D., Gautreau, A., Arpin, M., Gschmeissner, S., Verveer, P.J., Bastiaens, P.I., et al. (2001). Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility. The EMBO journal 20, 2723-2741.
Nguyen, M., Arkell, J., and Jackson, C.J. (2001). Human endothelial gelatinases and angiogenesis. The international journal of biochemistry & cell biology 33, 960-970.
Nishizuka, Y. (1992). Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258, 607-614.
Nolan, C.P., and Abrey, L.E. (2005). Leptomeningeal metastases from leukemias and lymphomas. In Leptomeningeal Metastases (Springer), pp. 53-69.
O'Toole, E.A., van Koningsveld, R., Chen, M., and Woodley, D.T. (2008). Hypoxia induces epidermal keratinocyte matrix metalloproteinase-9 secretion via the protein kinase C pathway. Journal of cellular physiology 214, 47-55.
Osiak, A.E., Zenner, G., and Linder, S. (2005). Subconfluent endothelial cells form podosomes downstream of cytokine and RhoGTPase signaling. Experimental cell research 307, 342-353.
Padró, T., Ruiz, S., Bieker, R., Bürger, H., Steins, M., Kienast, J., Büchner, T., Berdel, W.E., and Mesters, R.M. (2000). Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia. Blood 95, 2637-2644.
Paietta, E., Mittermayer, K., and Schwarzmeier, J.D. (1979). [Prognostic significance of the cyclic AMP concentration in acute leukemias]. Acta medica Austriaca 6, 231-233.
Pei, R., Cao, J., Ma, J., Zhang, P., Liu, X., Du, X., Chen, D., Sha, K., Chen, L., Li, S., et al. (2012). Long term curative effects of sequential therapy with all-trans retinoic acid, arsenious oxide and chemotherapy on patients with acute promyelocytic leukemia. Hematology 17, 311-316.
Peiretti, F., Bernot, D., Lopez, S., Bonardo, B., Deprez‐Beauclair, P., Juhan‐Vague, I., and Nalbone, G. (2003). Modulation of PAI‐1 and proMMP‐9 syntheses by soluble TNFα and its receptors during differentiation of the human monocytic HL‐60 cell line. Journal of cellular physiology 196, 346-353.
Perez-Atayde, A.R., Sallan, S.E., Tedrow, U., Connors, S., Allred, E., and Folkman, J. (1997). Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. The American journal of pathology 150, 815-821.
Pfaff, M., and Jurdic, P. (2001). Podosomes in osteoclast-like cells: structural analysis and cooperative roles of paxillin, proline-rich tyrosine kinase 2 (Pyk2) and integrin alphaVbeta3. J Cell Sci 114, 2775-2786.
Poincloux, R., Vincent, C., Labrousse, A., Castandet, J., Rigo, M., Cougoule, C., Bordier, C., Le Cabec, V., and Maridonneau-Parini, I. (2006). Re-arrangements of podosome structures are observed when Hck is activated in myeloid cells. European journal of cell biology 85, 327-332.
Pule, M.A., Gullmann, C., Dennis, D., McMahon, C., Jeffers, M., and Smith, O.P. (2002). Increased angiogenesis in bone marrow of children with acute lymphoblastic leukaemia has no prognostic significance. British journal of haematology 118, 991-998.
Purcell, W.T., Rudek, M.A., and Hidalgo, M. (2002). Development of matrix metalloproteinase inhibitors in cancer therapy. Hematology/oncology clinics of North America 16, 1189-1227.
Qiu, Q., Yang, M., Tsang, B.K., and Gruslin, A. (2004). EGF-induced trophoblast secretion of MMP-9 and TIMP-1 involves activation of both PI3K and MAPK signalling pathways. Reproduction 128, 355-363.
Ransjii, M. (1991). Protein kinase C activating phorbolesters enhance the cyclic AMP response to parathyroid hormone, forskolin and choleratoxin in mouse calvarial bones and rat osteosarcoma cells. Bioscience Reports.
Redondo-Munoz, J., Escobar-Diaz, E., Samaniego, R., Terol, M.J., Garcia-Marco, J.A., and Garcia-Pardo, A. (2006). MMP-9 in B-cell chronic lymphocytic leukemia is up-regulated by alpha4beta1 integrin or CXCR4 engagement via distinct signaling pathways, localizes to podosomes, and is involved in cell invasion and migration. Blood 108, 3143-3151.
Reifel-Miller, A.E., Conarty, D.M., Valasek, K.M., Iversen, P.W., Burns, D.J., and Birch, K.A. (1996). Protein kinase C isozymes differentially regulate promoters containing PEA-3/12-O-tetradecanoylphorbol-13-acetate response element motifs. The Journal of biological chemistry 271, 21666-21671.
Robinson, M.J., and Cobb, M.H. (1997). Mitogen-activated protein kinase pathways. Current opinion in cell biology 9, 180-186.
Rothenberg, M.L., Nelson, A.R., and Hande, K.R. (1999). New drugs on the horizon: matrix metalloproteinase inhibitors. Stem cells (Dayton, Ohio) 17, 237-240.
Sawicki, G., Matsuzaki, A., and Janowska-Wieczorek, A. (1998). Expression of the active form of MMP-2 on the surface of leukemic cells accounts for their in vitro invasion. J Cancer Res Clin Oncol 124, 245-252.
Schmalfeldt, B., Prechtel, D., Harting, K., Spathe, K., Rutke, S., Konik, E., Fridman, R., Berger, U., Schmitt, M., Kuhn, W., et al. (2001). Increased expression of matrix metalloproteinases (MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 7, 2396-2404.
Seftor, R.E., Seftor, E.A., Koshikawa, N., Meltzer, P.S., Gardner, L.M., Bilban, M., Stetler-Stevenson, W.G., Quaranta, V., and Hendrix, M.J. (2001). Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. Cancer Res 61, 6322-6327.
Selleri, C., Pane, F., Notaro, R., Catalano, L., Santoro, L.E., Luciano, L., Frigeri, F., Salvatore, F., and Rotoli, B. (1996). All-trans-retinoic acid (ATRA) responsive skin relapses of acute promyelocytic leukaemia followed by ATRA-induced pseudotumour cerebri. British journal of haematology 92, 937-940.
Shen, Z.X., Shi, Z.Z., Fang, J., Gu, B.W., Li, J.M., Zhu, Y.M., Shi, J.Y., Zheng, P.Z., Yan, H., Liu, Y.F., et al. (2004). All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America 101, 5328-5335.
Shibakura, M., Niiya, K., Kiguchi, T., Shinagawa, K., Ishimaru, F., Ikeda, K., Namba, M., Nakata, Y., Harada, M., and Tanimoto, M. (2002). Simultaneous induction of matrix metalloproteinase-9 and interleukin 8 by all-trans retinoic acid in human PL-21 and NB4 myeloid leukaemia cells. British journal of haematology 118, 419-425.
Shuvojit Moulik, Triparna Sen, Anindita Dutta, Aniruddha Banerji, Chinmoy Ghosh, Shamik Das, and Chatterjee, A. (2008). Phosphatidylinositol 3-Kinase and NF-kB Involved in Epidermal Growth Factor-Induced Matrix Metalloproteinase-9 Expression. J Cancer Mol 4, 55-60.
Simon, C., Goepfert, H., and Boyd, D. (1998). Inhibition of the p38 mitogen-activated protein kinase by SB 203580 blocks PMA-induced Mr 92,000 type IV collagenase secretion and in vitro invasion. Cancer Res 58, 1135-1139.
Soto-Guzman, A., Navarro-Tito, N., Castro-Sanchez, L., Martinez-Orozco, R., and Salazar, E.P. (2010). Oleic acid promotes MMP-9 secretion and invasion in breast cancer cells. Clinical & experimental metastasis 27, 505-515.
Sternlicht, M.D., and Werb, Z. (2001). How matrix metalloproteinases regulate cell behavior. Annual review of cell and developmental biology 17, 463-516.
Stetler-Stevenson, W.G. (1999). Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. The Journal of clinical investigation 103, 1237-1241.
Tang, S., Morgan, K.G., Parker, C., and Ware, J.A. (1997). Requirement for protein kinase C theta for cell cycle progression and formation of actin stress fibers and filopodia in vascular endothelial cells. The Journal of biological chemistry 272, 28704-28711.
Tatin, F., Varon, C., Genot, E., and Moreau, V. (2006). A signalling cascade involving PKC, Src and Cdc42 regulates podosome assembly in cultured endothelial cells in response to phorbol ester. J Cell Sci 119, 769-781.
van Oostenbrugge, R.J., and Twijnstra, A. (1999). Presenting features and value of diagnostic procedures in leptomeningeal metastases. Neurology 53, 382-385.
Van Wart, H.E., and Birkedal-Hansen, H. (1990). The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proceedings of the National Academy of Sciences of the United States of America 87, 5578-5582.
Varon, C., Tatin, F., Moreau, V., Van Obberghen-Schilling, E., Fernandez-Sauze, S., Reuzeau, E., Kramer, I., and Genot, E. (2006). Transforming growth factor beta induces rosettes of podosomes in primary aortic endothelial cells. Molecular and cellular biology 26, 3582-3594.
Vihinen, P., and Kahari, V.M. (2002). Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. International journal of cancer Journal international du cancer 99, 157-166.
Volkov, Y., Long, A., McGrath, S., Ni Eidhin, D., and Kelleher, D. (2001). Crucial importance of PKC-beta(I) in LFA-1-mediated locomotion of activated T cells. Nature immunology 2, 508-514.
Vu, T.H., Shipley, J.M., Bergers, G., Berger, J.E., Helms, J.A., Hanahan, D., Shapiro, S.D., Senior, R.M., and Werb, Z. (1998). MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 93, 411-422.
Weaver, A.M. (2006). Invadopodia: specialized cell structures for cancer invasion. Clinical & experimental metastasis 23, 97-105.
Weiss, M.A., and Warrell, R.P., Jr. (1994). Two cases of extramedullary acute promyelocytic leukemia. Cytogenetics, molecular biology, and phenotypic and clinical studies. Cancer 74, 1882-1886.
Westermarck, J., and Kahari, V.M. (1999). Regulation of matrix metalloproteinase expression in tumor invasion. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 13, 781-792.
Wheeler, A.P., Smith, S.D., and Ridley, A.J. (2006). CSF-1 and PI 3-kinase regulate podosome distribution and assembly in macrophages. Cell motility and the cytoskeleton 63, 132-140.
Wiernik, P.H., De Bellis, R., Muxi, P., and Dutcher, J.P. (1996). Extramedullary acute promyelocytic leukemia. Cancer 78, 2510-2514.
Woo, J.H., Lim, J.H., Kim, Y.H., Suh, S.I., Min, D.S., Chang, J.S., Lee, Y.H., Park, J.W., and Kwon, T.K. (2004). Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction. Oncogene 23, 1845-1853.
Xiao, L.J., Lin, P., Lin, F., Liu, X., Qin, W., Zou, H.F., Guo, L., Liu, W., Wang, S.J., and Yu, X.G. (2012). ADAM17 targets MMP-2 and MMP-9 via EGFR-MEK-ERK pathway activation to promote prostate cancer cell invasion. International journal of oncology 40, 1714-1724.
Yamaguchi, H., and Condeelis, J. (2007). Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochimica et biophysica acta 1773, 642-652.
Yamaguchi, H., Lorenz, M., Kempiak, S., Sarmiento, C., Coniglio, S., Symons, M., Segall, J., Eddy, R., Miki, H., Takenawa, T., et al. (2005). Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin. The Journal of cell biology 168, 441-452.
Zhao, Q., Tao, J., Zhu, Q., Jia, P.M., Dou, A.X., Li, X., Cheng, F., Waxman, S., Chen, G.Q., Chen, S.J., et al. (2004). Rapid induction of cAMP/PKA pathway during retinoic acid-induced acute promyelocytic leukemia cell differentiation. Leukemia 18, 285-292.
Zhou, Z., Apte, S.S., Soininen, R., Cao, R., Baaklini, G.Y., Rauser, R.W., Wang, J., Cao, Y., and Tryggvason, K. (2000). Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proceedings of the National Academy of Sciences of the United States of America 97, 4052-4057.
Zimmerman, N.P., Roy, I., Hauser, A.D., Wilson, J.M., Williams, C.L., and Dwinell, M.B. (2013). Cyclic AMP regulates the migration and invasion potential of human pancreatic cancer cells. Molecular carcinogenesis.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2020-09-10起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2020-09-10起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw