RSPO2 enriches LGR5(+) spheroid colon cancer stem cells and promotes its metastasis by epithelial-mesenchymal transition.

Abstract

Colon cancer stem cells (CCSCs) account for the tumorigenicity of colon cancer and promote its progression and metastasis. RSPO2, the agonist of canonical Wnt/beta-catenin pathway and serves as the growth factor of intestinal stem cells (ISCs), is considered playing an important role in CCSCs. However, the specific function of RSPO2 in CCSCs remains unclear. In this study, we demonstrated that RSPO2 was highly expressed in CCSCs-enriched HCT116 spheroid cells. Elevates the concentration of RSPO2 in medium in favor of enriching the LGR5(+) cells and increasing the LGR5 expression in HCT116 spheroid cells, meanwhile silencing of RSPO2 by small interfering RNA inhibits LGR5 expression in HCT116 spheroid cells. In addition, RSPO2 promotes spheres formation but has little effect on the proliferation of HCT116 spheroid cells in vitro. Moreover, RSPO2 also promotes the invasion of HCT116 spheroid cells through enhancing Epithelial-mesenchymal transition (EMT). These findings suggests that RSPO2 is a potential growth factor for CCSCs, helps enriching the CCSCs by serum-free DMEM/F12 medium (SFM) culture and plays a vital role in the metastasis of colon cancer.