Oncol Rep. 2018 Jul 27. doi: 10.3892/or.2018.6605. [Epub ahead of print]

Mesothelial cells facilitate cancer stem‑like properties in spheroids of ovarian cancer cells.

Shishido A¹, Mori S², Yokoyama Y¹, Hamada Y¹, Minami K³, Qian Y¹, Wang J¹, Hirose H¹, Wu X¹, Kawaguchi N¹, Nagumo S¹, Matsuura N¹, Yamamoto H¹.

Abstract

Ovarian cancer is characterized by widespread peritoneal dissemination with ascites. Spheroids observed in the ascites of ovarian cancer patients are a mixture of cancer cells and mesothelial cells. In the present study, we evaluated whether mesothelial cells exfoliated from the peritoneum facilitate tumor spheroid formation and give rise to cancer stem‑like properties in ovarian cancer cells. Spheroids from the CAOV3 and A2780 ovarian cancer cell lines grew much larger in co‑culture with mesothelial cells than in monoculture under 3D conditions. The spheroids in co‑culture displayed high Ki‑67 expression in the peripheral zone and low expression in the central zone area. The expression of CD133 emerged in the inner portion of spheroids at later time‑points (96 and 168 h), indicating that cancer cells expanded to the inner spheroid and acquired stem cell‑properties. The mRNA levels of cancer stem cell markers Dclk‑1, CD44 and Bmi‑1 significantly increased in co‑cultured CAOV3 and mesothelial cells compared to CAOV3 cells alone. Furthermore, the mesothelial cells promoted the tumorigenesis and growth of the CAOV3 cells in a mouse xenograft model compared to cancer cells alone. In conclusion, mesothelial cells promoted spheroid formation by ovarian cancer cells and facilitated cancer stem‑like properties.