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系統識別號 U0026-2707201422353400
論文名稱(中文) 探討Eps8在巨噬細胞所刺激的大腸癌細胞爬行中所扮演的角色
論文名稱(英文) The role of Eps8 in macrophage-stimulated colon cancer cell migration
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 102
學期 2
出版年 103
研究生(中文) 潘郁辰
研究生(英文) Yu-Chen Pan
學號 S26011091
學位類別 碩士
語文別 英文
論文頁數 57頁
口試委員 指導教授-呂增宏
口試委員-凌斌
口試委員-馬明琪
口試委員-張雋曦
中文關鍵字 Eps8  THP-1巨噬細胞  SW480 大腸癌細胞  細胞移行 
英文關鍵字 Eps8  THP-1 cell  SW480 cell  cell migration 
學科別分類
中文摘要 巨噬細胞調控在腫瘤微環境會影響癌症的發展。過去的研究指出Eps8會參與巨噬細胞中脂多醣所誘導的吞噬作用。已知不正常的Eps8 表達在癌症的形成中可能扮演重要的角色,因此我們想要了解Eps8 在巨噬細胞對癌細胞惡化扮演的角色。PMA誘導單核球分化成巨噬細胞。伴隨著分化的過程,Eps8的表現及Src的活性皆有上升的情形。而進一步的給予LPS(脂多醣)的刺激同樣的也會促使其上升。Eps8的衰減會使PMA與LPS處理下的THP-1 細胞的伸展及吞噬能力被抑制。因此,就如同在小鼠巨噬細胞中ㄧ樣,Eps8在人類巨噬細胞也同樣扮演一個重要的角色。更進ㄧ步,在缺氧環境下THP-1巨噬細胞會促進周邊SW480細胞的移動。壓制Eps8 表達會減少THP-1對SW480大腸癌細胞的移動能力。採用THP-1 細胞條件培養液也可以看到促進SW480的移動能力,而Eps8在THP-1巨噬細胞條件培養液的作用中也扮演重要的角色。此外,伴隨著SW480細胞移動能力的上升,SW480細胞中的FAK及Src活性也隨著上升。綜合上述,這些發現告訴我們Eps8 確實參與在巨噬細胞調控大腸癌細胞的進展。
英文摘要 Macrophages in tumor microenvironment affects cancer development and progression. Previous study indicated that Eps8 participated in LPS-induced phagocytosis in macrophages. Given that abnormal expression of Eps8 contributes to the malignancy of various types of cancer, we want to address the importance of Eps8 in promoting cancer progression. Accompanying with THP-1 differentiating from monocytes into macrophages, the expressions of Eps8 as well as Src kinase activity are elevated. LPS treatment further elevates their expression. Attenuation of Eps8 abolished cell spreading and phagocytic activity in LPS- treated THP-1 macrophages. Thus, like in RAW264.7 cells, Eps8 plays an important role in the innate immunity in human macrophages. Interestingly, we discovered that silencing Eps8 in THP-1 macrophage reduced cell motility in both SW480 and THP-1 cells under co-cultured condition. Besides, THP-1-derived conditioned medium enhanced the cell motility in SW480 cells while silencing Eps8 in THP-1 cells abolished this effect. Similar phenomenon was observed in hypoxia condition. Western blotting indicates Eps8 participates in the activation of FAK and Src activity under hypoxia condition. These findings reveal that Eps8 might involve in macrophages promoting colon cancer progression.
論文目次 Abstract 1
Abstract in Chinese 3
致謝 4
Contents 6
Figures of contents 7
Abbreviations 9
Introduction 10
Materials and Method 18
Results 25
Discussion 30
References 34
Appendix 56
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