阻断间充质干细胞构造转移灶肿瘤微环境减少结直肠癌术后肝转移的机制研究

项目名称： 阻断间充质干细胞构造转移灶肿瘤微环境减少结直肠癌术后肝转移的机制研究

项目编号： No.81460379

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 谭浩翔

作者单位： 广西中医药大学

项目金额： 47万元

中文摘要： 肿瘤微环境(TME)影响肿瘤多种特性。已发现由原发灶癌细胞协助产生premetastatic niche是转移灶TME构成的开始，抑制niche产生可减少肿瘤转移形成。虽然手术切除原发灶后已无后续循环肿瘤细胞及niche来源，结直肠癌(CRC)术后出现肝转移的原因可能在于残留并已获得niche的循环肿瘤细胞构造TME后形成转移灶所致。因此抑制转移灶TME的形成，可能是减少CRC术后肝转移的重要方法。 新近发现MSCs在CRC原发灶TME构成中可分化为类肿瘤相关成纤维细胞(CAFs)以及MSCs与CAFs聚集于CRC肝转移灶的现象，MSCs可能是CRC术后肝转移灶TME构成的关键。 本课题通过探讨人CRC不同转移特性细胞株与MSCs及HSCs的体内外相互关系，最终证实阻断MSCs构造转移灶TME可减少CRC术后肝转移，并阐明MSCs在CRC术后肝转移灶TME中的作用机制。

中文关键词： 结直肠癌；肝转移；间充质干细胞；肿瘤微环境

英文摘要： Tumor microenvironment(TME) effect on the biological behavior of tumor. The formation of premetastatic niche for which the primary tumor cells offer assistance was the initial step of TME in tumor metastasis. Inhibition of the premetastatic niche could decrease tumor metastasis. Although circulating tumor cells (CTCs) and the premetastatic niche were removed by resection of primary tumor, liver metastasis of colorectal cancer(CRC) could still be occurred after operation. The residual CTCs with the premetastatic niche which had produced by the primary tumor before operation kept the ability to begin the process of tumor metastasis in liver. Inhibition of the metastatic TME formation could be an important method for the colorectal cancer to decrease the liver metastasis. Some studies found mesenchymal stem cells(MSCs) could be differentiated into Cancer-associated fibroblasts(CAFs) in primary TME of CRC. MSCs and CAFs also proved to be gathered in liver metastasis of CRC. MSCs may be the most important cells in the metastasis TME of CRC. Our study try to discuss the relationship among human CRC cell lines, MSCs and HSCs in vivo and in vitro, the role of MSCs in the metastasis TME of CRC, and the mechanism for CRC liver metastasis suppressed by MSCs.

英文关键词： colorectal cancer;liver metastasis;mesenchymal stem cells;tumor microenvironment