Abstract
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.
Highlights
Colorectal cancer is the third leading cause of cancer deaths worldwide, and the 5-year relative survival rate is only 53.8–65.2% despite diagnostic and therapeutic advances [1,2]
The proportion of the CD133 positive cells was found to be less than 1% in parental cell lines, but more than 80% observed in spheroid cells (Figure 2)
When the colonospheres were subjected to immunofluorescence staining for Lgr5, obvious Lgr5 staining was observed on the the surface of most spheroid cells indicating the presence of cancer stem cells (CSCs) in colonosphere (Figure 2)
Summary
Colorectal cancer is the third leading cause of cancer deaths worldwide, and the 5-year relative survival rate is only 53.8–65.2% despite diagnostic and therapeutic advances [1,2]. Increasing evidence suggests that tumor initiation and metastases are dependent on a small sub-population of tumor cells termed cancer stem cells (CSCs) bearing infinite self-renewal potential and the capacity to differentiate into diverse populations comprising a tumor [3]. According to this model, cancer stem cells were found to sustain carcinogenesis, metastasis, and recurrence of colorectal cancer. Increasing researches have reported that the non-adherent, three-dimensional (3D) tumor spheres under serum-free conditions could efficiently enrich cancer stem cells [18,19,20] in vitro. This method was applied to enrich colon cancer stem cells in the present study
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