Adipocyte secreted factors enhance aggressiveness of prostate carcinoma cells

PLoS One. 2015 Apr 30;10(4):e0123217. doi: 10.1371/journal.pone.0123217. eCollection 2015.

Abstract

Obesity has been associated with increased incidence and risk of mortality of prostate cancer. One of the proposed mechanisms underlying this risk association is the change in adipokines expression that could promote the development and progression of the prostate tumor cells. The main goal of this study was to evaluate the effect of preadipocyte and adipocyte secretome in the proliferation, migration and invasion of androgen independent prostate carcinoma cells (RM1) and to assess cell proliferation in the presence of the adiposity signals leptin and insulin. RM1 cells were co-cultured in with preadipocytes, adipocytes or cultured in their respective conditioned medium. Cell proliferation was assessed by flow cytometry and XTT viability test. Cell migration was evaluated using a wound healing injury assay of RM1 cells cultured with conditioned media. Cellular invasion of RM1 cells co-cultured with adipocytes and preadipocytes was assessed using matrigel membranes. Preadipocyte conditioned medium was associated with a small increase in RM1 proliferation, while adipocytes conditioned media significantly increased RM1 cell proliferation (p<0.01). Adipocytes also significantly increased the RM1 cells proliferation in co-culture (p <0.01). Cell migration was higher in RM1 cells cultured with preadipocyte and adipocyte conditioned medium. RM1 cell invasion was significantly increased after co-culture with preadipocytes and adipocytes (p <0.05). Insulin also increased significantly the cell proliferation in contrast to leptin, which showed no effect. In conclusion, prostate carcinoma cells seem to be influenced by factors secreted by adipocytes that are able to increase their ability to proliferate, migrate and invade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Animals
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Culture Media, Conditioned / pharmacology
  • Flow Cytometry
  • Insulin / pharmacology
  • Leptin / pharmacology
  • Male
  • Mice
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology

Substances

  • Culture Media, Conditioned
  • Insulin
  • Leptin

Grants and funding

This study was supported by grants Fcomp-01-0124-FEDER-015893 of the Fundação para a Ciência e a Tecnologia (FCT) of Portugal to The Unit for Multidisciplinary Research in Biomedicine (UMIB) and by a research grant from the Sociedade Portuguesa de Endocrinologia Diabetes e Metabolismo (SPEDM) to Ângela Moreira. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.