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

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 (LI(LPA1)), PCNA (LI(PCNA)), MCM7 (LI(MCM7)), ubiquitin (LI(UBI)), apoptotic cells (LI(APO)), and p53 (LI(p53)); volume fraction of Bcl-2 (V(F)Bcl-2); and length of microvessels per unit of volume (L(V)MV/mm3). Data were analyzed using Student's t-test and Pearson correlation test. RESULTS: The LI(LPA1) 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 V(F)Bcl-2. Dysplastic lesions showed a significant increase of LI(p53). The length of microvessels per unit of volume was elevated in dysplastic acini. Statistically significant correlations were found only between LI(LPA1) and LI(UBI). 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.