由於轉移與抗藥性的發生，使得肺癌在台灣成為癌症相關死亡原因的第一位，雖然已有文獻指出鉑金類抗癌藥物合併治療可以讓非小細胞肺癌患者達到較好的預後，但仍然無法避免轉移或抗藥性產生。因此探討在腫瘤組織當中是否存在一群新穎的細胞群是很重要的課題，這群細胞可能同時具有較好的轉移能力與抗藥性，且是過去未曾被發現過的。在研究當中，選用了非小細胞肺癌的細胞株 H1299，並對它處理接近 LD50 之 Cisplatin 劑量，三天後收集含有懸浮細胞之上清液並離心，接著將這些細胞重新培養於無藥物之正常細胞培養液中。大部份上清液中是已經死亡的細胞，但仍然有極小部分之細胞可以重新貼附於培養皿中，增生並形成細胞群落。這群重新貼附的 (Reattached, R) 細胞具有四項重要的特色：失去細胞間黏著能力、較慢的生長速率、抗藥性、及轉移能力；此外 R 細胞可以在 soft agar中形成較大之細胞群落，顯示它們具有較好之腫瘤形成能力。最後發現這群細胞會高度表現 CD44 蛋白，一個位於細胞膜上的分子，扮演細胞間黏著的角色，也有文獻指出與癌細胞轉移有關。總體而言，在研究過程當中我們發現了一新穎肺癌細胞群，可能存在於異質性的腫瘤組織當中，且具有惡性的潛能。

Due to the occurrence of metastasis and resistance to therapy, lung cancer is the leading cause of cancer-related death in Taiwan. Platinum-based chemotherapy confers a better survival in patients with non-small cell lung cancer. However, the efficacy is still limited by acquired or intrinsic resistance of cells to the drug. Therefore, it is important to elucidate whether there is any kind of cell population with capability to metastasize and chemo-resist which has never been investigated previously. In this study, non-small cell lung cancer H1299 cells were treated with cisplatin at the dose of LD50 for 3 days and the suspended cells were collected to re-plated them in culture dishes without cisplatin treatment. A small portion of suspended cells were reattached, proliferated, and formed colonies. These “reattached” cells possess four critical features including loss of cell adhesion, slower proliferation rate, chemo-resistance, and higher metastatic ability. In addition, these reattached cells could form larger colonies in soft agar, indicating that the cells may harbor tumorigenesis potential. These cells also over-expressed CD44, a protein which is cell surface marker for cell-cell adhesion and prone to be involved in metastasis. Overall, our results demonstrate that a newly selected population of lung cancer cells may exist in the tumor mass and has malignant potential.

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