Periostin Secreted by Carcinoma-Associated Fibroblasts Promotes Ovarian Cancer Cell Platinum Resistance Through the PI3K/Akt Signaling Pathway

Technol Cancer Res Treat. 2020 Jan-Dec:19:1533033820977535. doi: 10.1177/1533033820977535.

Abstract

Periostin (POSTN) is a protein secreted by mesenchymal cells. Periostin is upregulated in several cancer types and overexpression is associated with poor prognosis. However, the functional role and molecular underpinnings of periostin in epithelial ovarian cancer (EOC) is unknown. In the present study, periostin was found to be significantly upregulated in EOC stroma. Functional studies revealed that periostin could decrease cisplatin (DDP)-induced apoptosis in EOC. Periostin led to DDP resistance in EOC cells, potentially through the PI3K/Akt signaling pathway. We generated periostin-overexpressing fibroblasts and found that EOC cells were resistant to DDP when co-cultured with periostin-overexpressing fibroblasts. The findings of the present study indicated that periostin secreted by cancer-associated stromal cells may be a potential therapeutic target for EOC.

Keywords: apoptosis; carcinoma-associated fibroblasts; chemotherapy resistance; ovarian cancer; periostin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cancer-Associated Fibroblasts / metabolism*
  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / metabolism
  • Cell Adhesion Molecules / biosynthesis*
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Databases, Genetic
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Profiling
  • Humans
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Platinum / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction* / drug effects

Substances

  • Antineoplastic Agents
  • Cell Adhesion Molecules
  • POSTN protein, human
  • Platinum
  • Proto-Oncogene Proteins c-akt
  • Cisplatin