Lysophosphatidic acid‐induced expression of periostin in stromal cells: Prognoistic relevance of periostin expression in epithelial ovarian cancer

Lysophosphatidic acid (LPA) is a bioactive lipid crucial for the initiation and progression of ovarian cancer. Identification of LPA‐induced biomarkers is necessary for predicting prognosis of ovarian cancer patients. Here we report periostin, an extracellular matrix protein, as an LPA‐induced protein in stromal cells and as a prognostic marker in patients with epithelial ovarian cancer (EOC). In human EOC tissues, periostin was mainly expressed in cancer‐associated stromal fibroblasts, but not in cancer cells. The expression levels of periostin highly correlated with poor survival and tumor recurrence of ovarian cancer patients. Treatment of human adipose tissue‐derived stromal cells with LPA or conditioned media from human ovarian adenocarcinoma cell lines, such as SK‐OV‐3 and OVCAR‐3, induced expression of periostin. The periostin expression induced by cancer‐conditioned media was abrogated by silencing of the LPA receptor 1 expression using small hairpin RNA lentivirus. Recombinant periostin stimulated adhesion and invasion of SK‐OV‐3 human ovarian adenocarcinoma cells and induced expression of matrix metalloprotease‐2 in the cancer cells. These results suggest that LPA is associated with the expression of periostin in cancer‐associated fibroblasts of EOC.