Department of Gastrointestinal Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
PLoS One. 2012;7(6):e39069. doi: 10.1371/journal.pone.0039069. Epub 2012 Jun 26.
Although some studies described the characteristics of colon cancer stem cells (CSCs) and the role of endothelial progenitor cells (EPCs) in neovascularization, it is still controversial whether an interaction exists or not between CSCs and EPCs. In the present study, HCT116 and HT29 sphere models, which are known to be the cells enriching CSCs, were established to investigate the roles of this interaction in development and metastasis of colon cancer. Compared with their parental counterparts, spheroid cells demonstrated higher capacity of invasion, higher tumorigenic and metastatic potential. Then the in vitro and in vivo relationship between CSCs and EPCs were studied by using capillary tube formation assay and xenograft models. Our results showed that spheroid cells could promote the proliferation, migration and tube formation of EPCs through secretion of vascular endothelial growth factor (VEGF). Meanwhile, the EPCs could increase tumorigenic capacity of spheroid cells through angiogenesis. Furthermore, higher microvessel density was detected in the area enriching cancer stem cells in human colon cancer tissue. Our findings indicate that spheroid cells possess the characteristics of cancer stem cells, and the coaction of CSCs and EPCs may play an important role in the development of colon cancer.
虽然一些研究描述了结肠癌干细胞(CSCs)的特征和内皮祖细胞(EPCs)在新生血管形成中的作用,但 CSCs 和 EPCs 之间是否存在相互作用仍存在争议。在本研究中,建立了已知富含 CSCs 的 HCT116 和 HT29 球体模型,以研究这种相互作用在结肠癌发展和转移中的作用。与亲本细胞相比,球体细胞表现出更高的侵袭能力、更高的致瘤性和转移潜能。然后通过毛细血管形成试验和异种移植模型研究了 CSCs 和 EPCs 之间的体外和体内关系。我们的结果表明,球体细胞通过分泌血管内皮生长因子(VEGF)促进 EPCs 的增殖、迁移和管形成。同时,EPCs 可通过血管生成增加球体细胞的致瘤能力。此外,在富含人类结肠癌组织中癌症干细胞的区域检测到更高的微血管密度。我们的研究结果表明,球体细胞具有癌症干细胞的特征,CSCs 和 EPCs 的共同作用可能在结肠癌的发展中起重要作用。