The advance in the establishment of cell lines from clinical cancer samples: based on the cancer stem cell theory

临床癌症样本细胞系建立研究进展：基于癌症干细胞理论

• 批准号: 22591406
• 负责人: KAN Takatsugu
• 金额: $ 2.91万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591406/
• 关键词: 癌; 培養; 癌幹細胞

Although previous reports have shown that colon cancer-initiating cells, cancer stem cells, were enriched in CD133^<+>cell population, the potential ability of CD133^<->colon cancer cells introduced by mesenchymal cells to give rise to tumor formation has not ever been described. We have investigated the role of human mesenchymal cells on cancer initiation as the potential of cancer stem cell. CD133^<+>HCT116 cells, (CD133 positive rate is about 30%), at only 1.0×10^<3>initiated the tumor formation subcutaneously in NOD/SCID mice, while CD133^<->cells at 1.0×10^<5>could not in vivo. However, we found that CD133^<->cells, when mixed with human hepatic stellate cells, initiated tumor formation at only 1.0×10^<3>. Moreover, the tumor formation in vivo and colony formation in vitro was suppressed by the SDF-1 inhibitor, AMD3100, leading to that the potential of cancer initiation in CD133^<->HCT116 cells was introduced by SDF-1/CXCR4 axis. In conclusion, the potential of colon cancer stem cell, even in CD133^<->cells, might be led by the mesenchymal cells, especially in liver metastasis.

尽管之前的报道表明结肠癌起始细胞、癌症干细胞在CD133^+细胞群中富集，但间充质细胞引入的CD133^-结肠癌细胞引起肿瘤形成的潜在能力尚未被描述。我们研究了人类间充质细胞作为癌症干细胞的潜力在癌症发生中的作用。仅1.0×10^<3>的CD133^+HCT116细胞(CD133阳性率约为30％)在NOD/SCID小鼠皮下启动肿瘤形成，而1.0×10^<5>的CD133^<-细胞在体内则不能形成肿瘤。然而，我们发现CD133^<->细胞与人肝星状细胞混合时，仅在1.0×10^<3>时就开始肿瘤形成。此外，SDF-1抑制剂AMD3100抑制体内肿瘤形成和体外集落形成，导致SDF-1/CXCR4轴引入CD133^<->HCT116细胞中癌症起始的潜力。总之，结肠癌干细胞的潜力，即使是CD133^-细胞，也可能是由间充质细胞主导的，尤其是在肝转移中。