近年來研究已證實腫瘤幹細胞是產生惡性腫瘤的元兇。腫瘤幹細胞是具多種功能性，能自我更新並不斷地增殖、生長成不同型態的腫瘤細胞，並有研究指腦腫瘤出癌症幹細胞會表現一種名為CD133的胞外穿膜蛋白質(或稱promonin-1)。然而，CD133在腫瘤細胞癌化上是否帶有生理特性仍未清楚地證實。本實驗室具有兩種不同來源的大鼠膠質瘤細胞株C6，分別為C6 cloneA和C6 cloneB，兩種細胞都無法偵測到極低的CD133基因或蛋白表現。比較兩種細胞的增殖能力和遷移能力，C6 CloneA增殖速度遠快於C6 CloneB，但遷移速度則遠低於C6 Clone-B。然而，C6 cloneA植入大鼠腦部一個月後可明顯生成腫瘤，C6 cloneB並未形成明顯的腦腫瘤。本實驗利用增殖速度較慢的C6 CloneB作為研究癌化的模式細胞，利用慢病毒基因傳輸系統轉殖人類的CD133基因到C6 CloneB細胞株，離體實驗數據顯示表現人類CD133基因的C6細胞，其增殖及遷移能力有顯著性增加，並加強腫瘤的生成。進一步以Q-PCR偵測麩胺酸轉運蛋白mRNA的表現量，顯示穩定表現CD133後，膠質瘤細胞的麩胺酸轉運蛋白GLAST會降低，可推測腫瘤癌化是因為GLAST表現量下降造成胞外麩胺酸累積，形成具有神經毒性的環境，傷害了正常腦區的神經，使腫瘤走向癌化。
CD133不只可視為腦瘤幹細胞的標誌，本實驗經過穩定轉染後發現提升CD133表現後，膠質瘤細胞C6可能會經由降低麩胺酸轉運蛋白GLAST而導致膠質瘤細胞C6癌化的現象。

The small population of tumor stem cells (tumor SCs) found in malignant glioma is considered as tumor-initiating cells. CD133 (Prominin-1) is known as a cell surface marker found on multipotent stem cells, as well as tumor SCs. Nevertheless, the role of CD133 remains unclear. Here, we compared the proliferative rate and migration in the two clones of C6 glioma cell line (C6-A and C6-B), which have undetectable expression of CD133 mRNA and protein. The C6-A cells with the higher proliferative rate were found to induce tumor formation in rat cerebral cortex one month after intracerebral injection. No or smaller tumor formation was observed in the brain receiving the C6-B cells with the lower proliferative rate. Furthermore, the genetic modified C6-B cell line (hCD133133+-C6B) that was stably transduced by human CD133 using lentiviral gene delivery method was generated. The hCD133+-C6B cells showed an increase in cell migration when compared to that observed in C6 cells lacking hCD133 expression (C6-Puro). Moreover, we found that hCD133+-C6 cells formed aggressive tumor in the cerebral cortex. Q-PCR analysis indicated that overexpression of hCD133 significantly reduced the mRNA levels of Na+-dependent glutamate/aspartate transporter (GLAST), one of glial-predominant glutamate transporter, which may cause an accumulation of extracellular glutamate in tumor and induce neuroexcitotoxicity. Together, we suggest that hCD133 gene transduction promotes C6-induced tumor progression possibly via reduced expression of GLAST and increased cell invasion.

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