Expression of lysophosphatidic acid receptor 1 and relation with cell proliferation, apoptosis, and angiogenesis on preneoplastic changes induced by cadmium chloride in the rat ventral prostate

PLoS One. 2013;8(2):e57742. doi: 10.1371/journal.pone.0057742. Epub 2013 Feb 22.

Abstract

Background: Lysophosphatidic acid (LPA) is a phospholipid growth factor involved in cell proliferation, differentiation, migration, inflammation, angiogenesis, wound healing, cancer invasion, and survival. This study was directed to evaluate the immunoexpression of LPA-1, cell proliferation, apoptosis, and angiogenesis markers in preneoplastic lesions induced with cadmium chloride in rat prostate.

Methods: The following parameters were calculated in ventral prostate of normal rats and rats that received Cd in drinking water during 24 months: percentages of cells immunoreactive to LPA-1 (LILPA1), PCNA (LIPCNA), MCM7 (LIMCM7), ubiquitin (LIUBI), apoptotic cells (LIAPO), and p53 (LIp53); volume fraction of Bcl-2 (VFBcl-2); and length of microvessels per unit of volume (LVMV/mm3). Data were analyzed using Student's t-test and Pearson correlation test.

Results: The LILPA1 in dysplastic lesions and normal epithelium of Cd-treated rats was significantly higher than those in the control group. Markers of proliferation were significantly increased in dysplastic lesions, whereas some apoptotic markers were significantly decreased. No significant differences between groups were found in VFBcl-2. Dysplastic lesions showed a significant increase of LIp53. The length of microvessels per unit of volume was elevated in dysplastic acini. Statistically significant correlations were found only between LILPA1 and LIUBI.

Conclusions: Our results suggest that LPA-1 might be implicated in dysplastic lesions induced by cadmium chloride development. More studies are needed to confirm its potential contribution to the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cadmium Chloride / toxicity
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / physiology
  • Male
  • Microvessels / metabolism
  • Microvessels / pathology
  • Minichromosome Maintenance Complex Component 7 / genetics
  • Minichromosome Maintenance Complex Component 7 / metabolism
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / genetics
  • Precancerous Conditions / metabolism*
  • Precancerous Conditions / pathology*
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Prostate / blood supply
  • Prostate / drug effects
  • Prostate / metabolism*
  • Prostate / pathology*
  • Prostatic Neoplasms / blood supply
  • Prostatic Neoplasms / chemically induced
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Lysophosphatidic Acid / biosynthesis*
  • Receptors, Lysophosphatidic Acid / genetics
  • Receptors, Lysophosphatidic Acid / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitin / genetics
  • Ubiquitin / metabolism

Substances

  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Lysophosphatidic Acid
  • Tumor Suppressor Protein p53
  • Ubiquitin
  • MCM7 protein, rat
  • Minichromosome Maintenance Complex Component 7
  • Cadmium Chloride

Grants and funding

This study was supported in part by a financial grant from San Pablo-CEU University and Santander Bank (USP-BS-PPC04/2011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.