Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion

Cancer-associated fibroblasts (CAFs) are thought to play an essential role in cancer initiation and development. However, little research has been done to evaluate the role of CAFs in epithelial ovarian cancer (EOC) development. To address this issue, ninety-one specimens were immunostained with α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP) antibodies to quantify CAFs, and antibodies D2-40 and CD34 to evaluate the lymphatic vessel density (LVD) and microvessel density (MVD) of the lesions. We found there were no α-SMA or FAP positive fibroblasts in normal ovary tissues. More CAFs were found in EOC than in borderline tumors and benign tumors (P < 0.01). Abundant CAFs in EOC were associated with advanced-stage disease (P = 0.002), the occurrence of lymph node metastases (P = 0.02) and omentum metastases (P < 0.0001), and increased LVD (P = 0.002) and MVD (P = 0.0004). CAFs isolated from EOC tissues induced more cancer cells to invade (P = 0.003) and migrate (P = 0.005) compared with normal fibroblasts (NFs) isolated from normal ovary tissues in vitro. Our data indicate that CAFs play a vital role in ovarian cancer progression and metastasis. Targeting CAFs as a therapeutic strategy against ovarian cancer is an intriguing concept that needs further study.