Co-expression of Lgr5 and CXCR4 characterizes cancer stem-like cells of colorectal cancer

// Weidong Wu 1, * , Jun Cao 1, * , Zhengyi Ji 1 , Jingjue Wang 2 , Tao Jiang 1 , Honghua Ding 2 1 Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China 2 Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China * These authors contributed equally to this work Correspondence to: Honghua Ding, email: dinghonghua_16@126.com , dinghonghua@163.com Tao Jiang, email: eric3837@sina.com Keywords: cancer stem cells (CSCs), colorectal cancer (CRC), Lgr5, CXCR4 Received: May 26, 2016 Accepted: October 26, 2016 Published: November 08, 2016 ABSTRACT Therapies designed to target cancer stem cells (CSCs) in colorectal cancer (CRC) may improve treatment outcomes. Different markers have been used to identify CSCs or CSC-like cells in CRC, but the enrichment of CSCs using these markers has yet to be optimized. We recently reported the importance of Lgr5-positive CRC cells in cancer growth. Here, we studied the possibility of using Lgr5 and CXCR4 as CSC markers for CRC. We detected high Lgr5 and CXCR4 levels in stage IV CRC specimens. Both high Lgr5 and CXCR4 levels were associated with poor prognosis in stage IV CRC patients. In vitro , Lgr5+CXCR4-, CXCR4+Lgr5- and Lgr5+CXCR4+ cells were purified in human CRC cell lines and examined for their CSC properties. We found that compared to the unsorted cells, CXCR4+Lgr5-, Lgr5+CXCR4-, and Lgr5+/CXCR4+ cells showed significantly greater cancer mass after subcutaneous transplantation, greater tumor sphere formation, higher resistance to chemotherapy, and higher incidence of tumor formation after serial adoptive transplantation into NOD/SCID mice. Taken together, our data suggest that the combined use of Lgr5 and CXCR4 may facilitate the enrichment of CSCs in CRC, and that treating Lgr5+/CXCR4+ CRC cells may improve the outcome of CRC therapy.