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

为乳腺癌患者制定癌症干细胞靶向治疗新策略

• 批准号: 18591439
• 负责人: KUBO Makoto
• 金额: $ 2.53万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591439/
• 关键词: cancer stem cell; breast cancer; anticancer-drug resistant; morphogenesis signais; side population; CD44+24-; low cell; estroren receptor

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.

据推测，肿瘤是由具有自我更新能力的癌症干细胞（CSC）产生的。分化潜力。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，因为癌组织包括分化的和未分化的组织;前者对抗癌药物敏感，后者与CSC一样对抗癌药物耐药。因此，本研究的目的之一是，我们确定CSC开发治疗CSC。(1)使用细胞分选仪从人乳腺癌细胞系富集Side群体（SP）和CD 44 +/CD 24-/low群体。(2)两个种群均被证实对紫杉醇具有耐药性。(3)我们发现SP细胞和CD 44 +24-/low细胞之间有很强的相关性。CD 44 +24-/low细胞比率通常在16%左右，但在SP中显著增加至46%。(4)实时荧光定量PCR和免疫印迹检测结果显示，CSC中高表达Wnt、Notch、Hedgehog [Hh]等形态发生信号。(5)我们证实了Hh和雌激素受体信号传导途径之间的串扰，其在乳腺癌中具有代表性（古贺K，et.等人，2008年）。(6)本室研制的Hh信号通路受体Patched 1抗体可有效抑制SP细胞和CD 44 +24-/low细胞的生长。因此，我们的结论是，Hh信号通路是必不可少的乳腺癌细胞是抗癌药物耐药。

项目成果

抗Patched1抗体による乳癌の分子標的治療の可能性

使用抗 Patched1 抗体对乳腺癌进行分子靶向治疗的可能性

• 发表时间: 2007
• 作者: Koga;K;Kubo;M;Katano;M;et. al.;久保 真
• 通讯作者: 久保 真

乳癌-基礎・臨床研究のアップデート

乳腺癌 - 基础和临床研究更新

• 发表时间: 2007
• 作者: Koga;K;Kubo;M;Katano;M;et. al.;久保 真;久保 真
• 通讯作者: 久保 真

herapeutic A possible therapeutic application of inhibitors of hedgehog signaling for patients with estrogen receptor-negative breast cancer

刺猬信号抑制剂对雌激素受体阴性乳腺癌患者的可能治疗应用

• 发表时间: 2008
• 期刊: Anticancer Res (In press)
• 作者: Kameda;C;Nakamura;M;Koga;K;Tanaka;H;Akiyoshi;T;Sato;N;Kubo;M;Tanaka;M;Katano;M
• 通讯作者: M

Hedgehogシグナルを利用した癌分子標的治療

利用 Hedgehog 信号进行癌症分子靶向治疗

• 发表时间: 2007
• 期刊: 癌と化学療法 34(12)
• 作者: 中村 雅史;他
• 通讯作者: 他

Novel link between estrogen receptor α and hedgehog pathway in breast cancer

• 发表时间: 2008-03
• 期刊: Anticancer Research
• 影响因子: 2
• 作者: Kenichiro Koga;Masafumi Nakamura;H. Nakashima;Takashi Akiyoshi;M. Kubo;N. Sato;S. Kuroki;M. Nomura;Masao Tanaka;M. Katano