Co-expression of Lgr5 and CXCR4 characterizes cancer stem-like cells of colorectal cancer.
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.
Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Weidong
W
Wu
Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Jun
J
Cao
Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Zhengyi
Z
Ji
Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Jingjue
J
Wang
Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Tao
T
Jiang
Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Honghua
H
Ding
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018938:Caco-2 Cells; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; C116884:LGR5 protein, human; D009944:Organoplatinum Compounds; D019718:Receptors, CXCR4; D043562:Receptors, G-Protein-Coupled; D000077150:Oxaliplatin; D005472:Fluorouracil
CXCR4; Lgr5; cancer stem cells (CSCs); colorectal cancer (CRC)