以人類鱗狀癌症細胞株A431探討腫瘤幹細胞與癌侵襲之相關性研究

鱗癌細胞 ( squamous cell carcinoma; SCC), 例如，口腔鱗狀細胞癌 (oral squamous cell carcinoma) 為一種增長快速的惡性腫瘤。儘管近幾年在治療方式有重大的突破，口腔鱗狀癌細胞的復發率仍然很高。幾項研究報告指出口腔鱗狀癌細胞中含有特定的癌症幹細胞cancer stem cells; CSCs）。此現象應與上皮-間葉移轉(epithelial-mesenchymal transition)有關。上皮-間葉移轉與腫瘤形成有關，癌症幹細胞較非致瘤癌細胞有能力形成腫瘤。然而，具有高增殖和遷移特性的癌症幹細胞是否與鱗癌細胞侵襲和轉移有關較少被探討，其機轉亦需做更深入的研究。我們的研究假設為癌症幹細胞的增加會導致(口腔)鱗癌細胞的侵襲和轉移。在這項研究中，我們使用培養來自人類鱗癌細胞的A431細胞株。經由細胞連續稀釋及繼代培養出單細胞群落，並根據使用流式細胞儀偵測Oct-4，Nanog和CD44三種幹細胞表達基因特性及細胞自我更新的能力特性，區分出三個次群組的A431細胞株分別為混合、中度及主要癌症幹細胞組。接著使用包覆基質膠之轉移盤來觀察各群組細胞的入侵能力，以了解鱗癌細胞中癌症幹細胞群是否具有高增殖和遷移的特性。此外，低侵入性與侵入組群的A431次細胞組群的與上皮-間葉移轉有關之基因表現也被探討。本研究所區分出的三個次群組A431細胞株可用於癌浸潤，轉移，藥物耐受度高以及抗放射線、惡性及高復發率之口腔鱗狀癌細胞相關研究。這項研究有助於了解上皮-間葉移轉與鱗癌細胞的浸潤能力之相關性，以及特定的分子的表現也許有助於判斷鱗癌細胞，例如口腔鱗狀標癌之惡化程度。此研究對於尋找口腔鱗狀癌細胞病患之診斷和癒後評估之生物標誌將有所幫助。

關鍵字

鱗狀癌細胞,癌幹細胞,

並列摘要

Squamous cell carcinoma (SCC) including oral squamous cell carcinoma (OSCC) is one of the fastest growing malignant tumors. Despite major breakthrough in treatment modalities, OSCC remains one of the cancers with high recurrent incidence. Several studies have reported that OSCC contains a sub-group of cancer stem cells (CSCs). CSCs have the ability to form tumors as compared to non-tumorigenic cancer cells. The SCCs are transformed epithelial cells. Previous studies suggested that most OSCC of head and neck are caused by dysfunctional interaction between mesenchymal and epithelial elements (epithelial-mesenchymal transition, EMT) that may be associated with deregulation of cell growth, differentiation, therefore aiding angiogenesis, and metastasis in the process. In addition, the high proliferation and migration characteristics of stem cell may correlate with invasion and metastasis of OSCC. We hypothesize that increased expressions of CSC may contribute the invasiveness and metastasis of SCC (or OSCC). In this study, we cultured A431 cells, which are derived from human squamous cell carcinoma. Through the passages, we isolated three sub-populations of SCC with mixture, moderate and dominate CSC, according to the proportional expressions of three stemness / self-renewal genes, Oct-4, Nanog, and CD44 by flow cytometry. The ability of invasion of the sub-populations of SCC was investigated by the observation of cell migration in Matrigel coated trans-wells. In addition, the altered gene expressions in the most invasive subpopulation versus A431 mixture cells are identified. This study may help understand the relationship of EMT and tumor invasion and metastasis. It may be useful to identify potential markers for diagnosis and prognosis of high risk patients with OSCC.

並列關鍵字

Cancer stem cells, Squamous cell carcinoma, Epithelial Mesenchymal transition

參考文獻

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以人類鱗狀癌症細胞株A431探討腫瘤幹細胞與癌侵襲之相關性研究

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