Open AccessCD 44 variant 6 is correlated with peritoneal dissemination and poor prognosis in patients with advanced epithelial ovarian cancer
Author(s) -
Tjhay Francisca,
Motohara Takeshi,
Tayama Shingo,
Narantuya Dashdemberel,
Fujimoto Koichi,
Guo Jianying,
Sakaguchi Isao,
Honda Ritsuo,
Tashiro Hironori,
Katabuchi Hidetaka
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12765
Subject(s) - cd44 , ovarian cancer , metastasis , cancer stem cell , cancer , cancer research , medicine , cancer cell , pathology , oncology , biology , cell , genetics
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.