2012-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/696940摘要：無論在全世界或台灣，乳癌都是造成癌症死亡的主因，也是女性最常見的癌症。乳癌細胞有很多種分類，若依據細胞表面雌激素受體(ER)、孕激素受體(PR)和人表皮生長因子受體2(HER-2)表現的不同，乳癌細胞可分為管狀A 型(Luminal A)、管狀B 型(Luminal B)、HER2 過度表現型(HER2)、基底A 型(Basal A)、基底B 型(Basal B)，而不同類型的乳癌細胞有不同的生物特性與治療反應，也因為乳癌的複雜性增加了乳癌治療的困難度。而化療是治療乳癌最常用的方式之一，但抗藥性和癌症復發是仍待解決的重要議題。根據癌幹細胞(cancer stem cell)假說，癌幹細胞是癌細胞中一小群具有幹細胞特性、癌症形成能力，且對化療藥較具抗藥性的細胞，而這可能是治療乳癌的關鍵。乳腺球細胞(mammosphere)和側群細胞(side population)都被認為是乳癌幹細胞的指標，而我們發現側群細胞與乳腺球細胞只表現在管狀型細胞。為了瞭解側群細胞與乳腺球細胞之間的關係，我們測試側群細胞形成乳腺球細胞之能力並且分析乳腺球細胞中側群細胞的比例。結果發現，側群細胞比非側群細胞具有更高的乳腺球細胞形成能力，且乳腺球細胞比單層細胞具有更高的側群細胞比例，顯示出側群細胞中富含可形成乳腺球細胞的細胞。我們研究乳癌細胞株（MCF7）的側群細胞特性，發現它比非側群細胞(non-side population)表現較高的ABC 轉運蛋白(ABCG2)和幹細胞基因Notch-1,具較高的細胞簇(colony)形成能力，且對化療藥有較高的抗藥性，顯示出側群細胞確實具有癌幹細胞特性。此外，側群細胞的抗藥性會受到細胞外基質(extracellular matrix)影響而增高。由這些結果我們知道，乳腺球細胞和側群細胞適用於管狀型乳癌幹細胞之辨識，且這兩群細胞可能是互相重疊的，若能針對這兩群細胞研究治療方法，就能增加管狀型乳癌細胞之治療效果。<br> Abstract: Breast cancer is a leading cause of cancer-related death and is the most prevalent cancer amongwomen worldwide, including Taiwan. There are many classifications of breast cancer cells. Based on theexpressions of ER, PR, and HER2, breast cancer cells can be classified into Luminal A, Luminal B, HER2,Basal A, and Basal B subtypes. Because breast cancer is heterogeneous and complex that different types ofbreast cancer cells have different biological characteristics and respond differently to therapy, the treatmentin breast cancer is challenging. Chemotherapy is one of the common therapeutic strategies in breast cancer,but drug resistance and recurrence are important issue to solve. According to the cancer stem cell hypothesis,cancer stem cells are a small population with stem cell-like properties, tumor-initiating ability, and moreresistant to chemotherapy, and these may be critical in the treatment in breast cancer. Mammosphere andside population (SP) have been identified as candidates for breast cancer stem cells. We found that SP andmammosphere were more prevalent in the Luminal type than the Basal type breast cancer cells. Toinvestigate the relationship between SP and mammosphere, we performed SP analysis on mammospheresand mammosphere formation assay on SP cells, and the results showed that mammospheres had higher SPexpression than the monolayer cells. Furthermore, the SP had higher mammosphere formation ability thanthe NSP, suggesting that mammosphere-forming cells were enriched in SP cells. We investigated thecharacterizations of MCF7 SP cells, and we found they had higher ABCG2 and Notch-1 expressions, highercolony formation ability, and more resistant to chemotherapy than the non-side population (NSP), indicatingthat SP had cancer stem cell properties. Besides, the drug resistance of the SP could be increased onextracellular matrixes (ECMs). In conclusion, mammosphere and SP could identify the cancer stem cellpopulation in Luminal type breast cancer cells, and these two populations might be overlapping. Therapeuticstrategies targeting on these two populations may have significant effect on breast cancer treatment.癌幹細胞側群細胞乳腺球細胞抗藥性管狀基底cancer stem cellside populationmammospheredrug resistanceLuminalBasal