Human METCAM對鼻咽癌發展的可能影響及其扮演的功能

The putative roles of huMETCAM in modulating the development and progression of nasopharyngeal carcinoma

劉彥君(Yen-Chun Liu)

指導教授 ： 吳光哲

中原大學/工學院/生物科技研究所/碩士(2014年)

https://doi.org/10.6840/cycu201400062

摘要

鼻咽癌形成初期的分子機制仍然不清楚，在過去的研究中我們發現在鼻咽癌病人身上有出現細胞膜上的分子METCAM有出現異常表達的現象，在正常的鼻咽組織METCAM正常的表達，在鼻咽癌組織中卻發現METCAM的表達量下降的五倍多，這樣的現象表明在腫瘤形成的時候細胞膜上的分子就已經開始發生了改變，另一方面在鼻咽癌發生轉移 (metastasis)至遠處器官當中我們檢測了METCAM的表現卻發現METCAM的表達量上升了，這樣的現象似乎指示著METCAM的表達與鼻咽癌的發展有著密切的關係，因此我們轉染METCAM基因進入NPC-TW01衍自Type I鼻咽癌及NPC-TW04衍自Type II鼻咽癌兩株鼻咽癌細胞，在體內及體外進行實驗，結果發現METCAM的表現會抑制NPC-TW01的體外移動性及侵犯性實驗，在動物體內的腫瘤形成實驗是非常顯著的抑制腫瘤形成。相反的， NPC-TW04在體外實驗部分的發現是：METCAM的表現促進移動及侵犯能力，在體內的實驗是：促進腫瘤形成。我們認為最後的結論是：METCAM的表現在體內及體外的實驗中證實，在Type I 鼻咽癌細胞株NPC-TW01當中是一個腫瘤抑制基因。但在另一株細胞Type II 鼻咽癌細胞株NPC-TW04中卻可能是致腫瘤基因。初步的機制研究結果是METCAM的表現是抑制NPC-TW01之細胞生長、血管增生、及生存路徑，增進凋亡；而對NPC-TW04則是增進其細胞生長、血管增生、及生存路徑， 抑制凋亡。

關鍵字

鼻咽癌 ； METCAM/MCU18 ； 細胞黏附分子

並列摘要

METCAM, a cell adhesion molecular belong immunoglobulin-like gene superfamily, is located on the cell membrane glycoprotein. We have found in our past studies that METCAM has different functions in different cancers. METCAM expression promotes the progress of melanoma, breast and cancer and prostate cancer. On the other hand, METCAM expression suppresses ovarian cancer proliferation and metastasis. We found that METCAM expression in NPC patients is very interesting. METCAM is expressed in normal nasopharyngeal tissue, but decreases expression in nasopharyngeal carcinoma and re-expressed in metastatic lesions. To understand METCAM’s function in NPC, we transfected METCAM cDNA gene into NPC-TW01 established from Type I NPC and NPC-TW04 established from Type II NPC cells and isolated G418R clones to be tested in various in vitro and in vivo experiments. Our results showed that METCAM over-expression had no effect on in vitro cell growth rate of both NPC-TW01 and NPC-TW04 cell lines. METCAM over-expression in NPC-TW01 deceased in vitro cell migration and invasion ability, and inhibited in vivo tumor growth in athymic nude mice. But opposite results were obtained in NPC-TW04: METCAM expression in NPC-TW04 increased in vitro cell migration and cell invasion ability, and increased in vivo tumor growth in athymic nude mice. We suggest that METCAM is a tumor suppressor gene in Type I NPC-TW01, but as a tumor promoter gene in Type II NPC-TW04. Preliminary mechanistic studies showed that METCAM expression decreased NPC-TW01 proliferation, angiogenesis and survival pathway, but increased apoptosis, in contrast, it increased NPC-TW04 proliferation, angiogenesis and survival pathway, but decreased apoptosis.

並列關鍵字

Nasopharyngeal carcinoma ； Nude mice ； METCAM/MUC18 ； In vitro migration and invasion ； 3D basement menbrane culture

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