Development of the new strategy by cancer stem cell-targeted therapy for patients with breast cancer

已有假说认为肿瘤是由同时具有自我更新功能的肿瘤干细胞(CSC)产生的。和分化潜能。我们需要制定和建立CSC的治疗策略，以进行有效和持久的治疗，因为肿瘤组织包括分化组织和未分化组织，前者与CSC一样具有抗癌药物敏感性，后者具有抗癌药物耐药性。因此，本研究的一个目的是寻找CSC以开发治疗CSC的方法。(1)用细胞分选机对人乳腺癌细胞株的侧群(SP)和CD44+/CD24-/低群进行了浓缩。(2)两个种群均对紫杉醇产生抗性。(3)SP细胞与CD44+24-/Low细胞密切相关。CD44+24-/Low细胞比率通常在16%左右，但在SP中显著增加，达46%。(4)实时定量聚合酶链式反应和免疫印迹显示形态发生信号(Wnt、Notch、Hedgehog[HH])在CSC中高表达。(5)证实了HH与乳腺癌(Koga K，ET)中具有代表性的雌激素受体信号通路之间的串扰。艾尔2008年)。(6)本实验室研制的抗HH信号通路受体Patched1抗体能有效抑制SP细胞和CD44+24-/Low细胞的生长。因此，我们认为HH信号通路在抗癌耐药的乳腺CSC中是必不可少的。

It has been hypothesized that a tumor generates from cancer stem cells (CSC) possessing both self-renewal. and differentiation potential. We need to develop and establish therapeutic strategies for CSC to perform effective and persistent treatment, because the carcinoma tissue consists of both differentiated and undifferentiated one; the former is anticancer-drug sensitive and the latter is anticancer-drug resistant as CSC. Therefore, a purpose of this study is that we identify CSC to develop treatment for CSC. (1) The Side population (SP) and the CD44+/CD24-/lowpopulation were enriched using cell sorter from human breast carcinoma cell lines. (2) Both populations were confirmed to be resistant to Paclitaxel. (3) We found strong relation between SP cells and CD44+24-/low cells. The CD44+24-/low cells ratio is usually around 16%, but increases with 46% in the SP remarkably. (4) The morphogenesis signals (Wnt, Notch, Hedgehog [Hh]) were highly expressed in CSC by real-time PCR and Immuno-blotting. (5) We confirmed the crosstalk between the Hh and the estrogen receptor signaling pathway which was representative in the breast cancer (Koga K, et. al. 2008). (6) The growth of SP cells and CD44+24-/low cells was effectively suppressed by the antibody for Patched1, receptor of the Hh signaling pathway, which was developed in our department. Thus, we conclude that the Hh signaling pathway is essential for breast CSC which is anticancer-drug resistant.