Expression of Osteoblast-Specific Factor 2 (OSF-2, Periostin) Is Associated with Drug Resistance in Ovarian Cancer Cell Lines

Int J Mol Sci. 2019 Aug 13;20(16):3927. doi: 10.3390/ijms20163927.

Abstract

One of the main obstacles to the effective treatment of ovarian cancer patients continues to be the drug resistance of cancer cells. Osteoblast-Specific Factor 2 (OSF-2, Periostin) is a secreted extracellular matrix protein (ECM) expressed in fibroblasts during bone and teeth development. Expression of OSF-2 has been also related to the progression and drug resistance of different tumors. The present study investigated the role of OSF-2 by evaluating its expression in the primary serous ovarian cancer cell line, sensitive (W1) and resistant to doxorubicin (DOX) (W1DR) and methotrexate (MTX) (W1MR). The OSF-2 transcript (real-time PCR analysis), protein expression in cell lysates and cell culture medium (western blot), and expression of the OSF-2 protein in cell lines (immunofluorescence) were investigated in this study. Increased expression of OSF-2 mRNA was observed in drug-resistant cells and followed by increased protein expression in cell culture media of drug-resistant cell lines. A subpopulation of ALDH1A1-positive cells was noted for W1DR and W1MR cell lines; however, no direct co-expression with OSF-2 was demonstrated. Both drugs induced OSF-2 expression after a short period of exposure of the drug-sensitive cell line to DOX and MTX. The obtained results indicate that OSF-2 expression might be associated with the development of DOX and MTX resistance in the primary serous W1 ovarian cancer cell line.

Keywords: Osteoblast-Specific factor 2 (OSF-2); drug resistance; extracellular matrix (ECM); ovarian cancer.

MeSH terms

  • Aldehyde Dehydrogenase 1 Family / genetics
  • Aldehyde Dehydrogenase 1 Family / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics*
  • Extracellular Matrix Proteins / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Retinal Dehydrogenase / genetics
  • Retinal Dehydrogenase / metabolism

Substances

  • Antineoplastic Agents
  • Cell Adhesion Molecules
  • Extracellular Matrix Proteins
  • POSTN protein, human
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase