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研究生:游采紅
研究生(外文):Tasi Hong You
論文名稱:探討Mac-2bindingprotein於口腔癌細胞移動過程的角色
論文名稱(外文):The role of Mac-2 binding protein in oral cancer cell movement
指導教授:余兆松
指導教授(外文):J. S. Yu
學位類別:碩士
校院名稱:長庚大學
系所名稱:基礎醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
論文頁數:60
中文關鍵詞:Mac-2 BP口腔癌細胞移動
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Mac-2 BP是一個分子量約90,000的分泌性醣蛋白,過去已有許多研究顯示其於多種癌症中皆有過量表達的情形。盡管如此,至今仍不清楚Mac-2 BP於癌細胞中所扮演的角色。實驗室過去證實Mac-2 BP具有成為口腔癌生物標誌(biomarker)的潛力,並且於口腔癌細胞株OEC-M1中利用RNA干擾術建立了 Mac-2 BP 表現量下降之穩定細胞株。我們發現抑制細胞中Mac-2 BP的表現會降低細胞的移動能力。因此,我們期望能了解Mac-2 BP在口腔癌細胞移動中所扮演的角色。在本實驗中,我們發現於細胞外加入Mac-2 BP抗體會抑制OEC-M1細胞的移動能力,顯示出細胞外Mac-2 BP參與了細胞移動的過程。曾有研究證明 Mac-2 BP會透過integrin-b1與其他細胞外基質 (如fibronectin)交互作用來調節細胞貼附。因此我們推測Mac-2 BP可能參與由integrin-b1調節的 fibrillogenesis 過程。我們發現Mac-2 BP表現被抑制的細胞中含有較少量的integrin-b1,其fibronectin fibrils 的形成似乎也受到影響。最近研究指出在前列腺癌中Mac-2 BP或是其他細胞激素會誘導proMMP7表現,我們發現Mac-2 BP表現被抑制的細胞中proMMP7與某些細胞激素的表現量皆比對照組細胞低。綜合以上,我們推論Mac-2 BP透過調節OEC-M1與fibronectin間交互作用以及誘導proMMP7 表現而促進細胞移動與侵略的能力。
Mac-2 binding protein (Mac-2 BP) is a 90 kDa secreted glycoprotein reported to be over-expressed in many cancers. However, its role in cancer biology remains unclear. We previously identified Mac-2 BP as a potential biomarker of oral cancer, and generated Mac-2 BP knockdown cell clones in OEC-M1 cells, a Chinese oral epidermal carcinoma cell line. We found that knockdown of Mac-2 BP in OEC-M1 cells impaired its cell mobility. Here, we try to elucidate the role of Mac-2 BP in oral cancer cell movement. We found that addition of the antibodies against Mac-2 BP into the cultured OEC-M1 cells can block the cell migration, indicating that extracellular Mac-2 BP is involved in the cell migration process. It was reported that Mac-2 BP can mediate cell adhesion in an integrin-b1-dependent manner through interacting with other extracellular matrix including fibronectin. We hypothesize that Mac-2 BP may involve in the fibrillogenesis process mediated by integrin-b1. This notion is supported by our findings that the Mac-2 BP knockdown cells had a lower expression level of integrin-b1 and altered fibronectin fibrils formation. It is also known that Mac-2 BP or certain cytokines could induce promatrilysin (proMMP7) expression in prostate cancer cells. We found that the expression level of proMMP7 and some cytokines decreased in the Mac-2 BP knockdown cells vs. vector controls. These results suggest that Mac-2 BP could modulate cell migration through regulating the interaction between fibronectin and OEC-M1 cells and induce proMMP7 expression to promote cell invasion.
前言-------------------------------------------------- 01頁
材料與方法--------------------------------------------- 08頁
實驗結果----------------------------------------------- 18頁
討論-------------------------------------------------- 23頁
圖表-------------------------------------------------- 27頁
參考文獻----------------------------------------------- 42頁
附表與附錄--------------------------------------------- 48頁
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