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

Abstract

BackgroundLysophosphatidic 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.MethodsThe 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.ResultsThe 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.ConclusionsOur 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.

A Review of Molecular Events of Cadmium-Induced Carcinogenesis

“…The etiology of prostate cancer development is complex and is associated with a multitude of potential contributing factors (23, 42, 43) (Table 1). Experimental evidence has shown that long-term exposure of normal human prostate epithelial cells (RWPE-1) to Cd in culture transforms them to malignant phenotypes (19, 44).…”

“…Lysophosphatidic acid (LPA), a phospholipid growth factor involved in a variety of cellular processes such as proliferation, differentiation, migration, inflammation, angiogenesis, wound healing, cancer invasion and survival is one of the most investigated molecules in experimental models (55-57). Cd-treated rats showed significantly higher LPA-1 expression in dysplastic lesions compared with that in normal prostate epithelium in controls (42). In addition, LPA may induce proliferation and survival of androgen-independent prostate cancer cells (55).…”

Potential Ameliorative Effects of Qing Ye Dan Against Cadmium Induced Prostatic Deficits via Regulating Nrf-2/HO-1 and TGF-β1/Smad Pathways

“…Especially for prostate, Cd requires much less time than other toxicant to produce the malignantly transformation on normal prostate epithelial cells [8]. Moreover, Cd triggers the prostatic local inflammatory responses and fibrillar rearrangement, damages the prostatic balance of collagen deposition and degradation, and disturbs the homeostasis of proliferation and apoptosis [7, 9, 10]. Increased collagen deposition and prostatic fibrosis are critical factors for the development of lower urinary symptoms (LUTS) and urinary obstructive symptoms [11].…”

Epigenetic Modifications Due to Heavy Metals Exposure in Children Living in Polluted Areas

“…This is relevant to the human health as cadmium is ranked as carcinogen [ 4 ], and furthermore smoke interferes either with epithelial wound healing [ 5 ] and the antioxidant/oxidant balance [ 6 , 7 ]. Both these effects have been shown to be directly or indirectly affected by Cd exposure [ 8 , 9 ].…”