Pathological Roles of Prostaglandin E2-specific E-type Prostanoid Receptors in Hormone-sensitive and Castration-resistant Prostate Cancer

Anticancer Res. 2021 Sep;41(9):4333-4341. doi: 10.21873/anticanres.15238.

Abstract

Background/aim: Prostaglandin (PG) E2 mediates malignant aggressiveness by binding to four specific E-type prostanoid receptors (EP1R - 4R). This study aimed to clarify the pathological significance of EPRs in hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC).

Materials and methods: EP1R - 4R expression was examined in 102 HSPC and 27 CRPC specimens. The relationships between their expression and proliferation index (PI), apoptotic index (AI), and vascular endothelial growth factor (VEGF)-A expression were analyzed.

Results: EP4R expression in CRPC was significantly higher compared to that in HSPC, even in advanced disease (T3/4, N1, and/or M1). EP4R expression was significantly correlated with PI, AI, and VEGF-A expression in CRPC. Such significant relationships were not detected between EP1R - 3R and CRPC.

Conclusion: EP4R expression in CRPC was significantly higher than that in HSPC and was associated with cancer cell proliferation, apoptosis, and pro-angiogenetic potential.

Keywords: E-type prostanoid receptors EPRs); apoptosis; castration-resistant prostate cancer (CRPC); proliferation; vascular endothelial growth factor-A.

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Cell Survival
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Neoplasm Grading
  • Neoplasm Staging
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Prostatic Neoplasms, Castration-Resistant / pathology*
  • Receptors, Prostaglandin E, EP4 Subtype / metabolism*
  • Up-Regulation*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • PTGER4 protein, human
  • Receptors, Prostaglandin E, EP4 Subtype
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A