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Cancer stem cells ( CSC s) drive tumor initiation and metastasis in several types of human cancer. However, the contribution of ovarian  CSC s to peritoneal metastasis remains unresolved. The cell adhesion molecule  CD 44 has been identified as a major marker for  CSC s in solid tumors, including epithelial ovarian cancer.  CD 44 exists as a standard form ( CD 44s) and also as numerous variant isoforms ( CD 44v) generated by alternative  mRNA  splicing. Here we show that disseminated ovarian tumors in the pelvic peritoneum contain highly enriched  CD 44v6‐positive cancer cells, which drive tumor metastasis and are responsible for tumor resistance to chemotherapy. Clinically, an increased number of  CD 44v6‐positive cancer cells in primary tumors was associated with a shortened overall survival in stage  III – IV  ovarian cancer patients. Furthermore, a subpopulation of  CD 44v6‐positive cancer cells manifested the ability to initiate tumor metastasis in the pelvic peritoneum in an  in vivo  mouse model, suggesting that  CD 44v6‐positive cells show the potential to serve as metastasis‐initiating cells. Thus, the peritoneal disseminated metastasis of epithelial ovarian cancer is initiated by the  CD 44v6‐positive subpopulation, and  CD 44v6 expression is a biomarker for the clinical outcome of advanced ovarian cancer patients. Given that a distinct subpopulation of  CD 44v6‐positive cancer cells plays a critical role in peritoneal metastasis, definitive treatment should target this subpopulation of  CD 44v6‐positive cells in epithelial ovarian cancer.

CD 44 variant 6 is correlated with peritoneal dissemination and poor prognosis in patients with advanced epithelial ovarian cancer