Differential Effects of Leptin on the Invasive Potential of Androgen-Dependent and -Independent Prostate Carcinoma Cells

Abstract

Obesity has been linked with an increased risk of prostate cancer. The formation of toxic free oxygen radicals has been implicated in obesity mediated disease processes. Leptin is one of the major cytokines produced by adipocytes and controls body weight homeostasis through food intake and energy expenditure. The rationale of the study was to determine the impact of leptin on the metastatic potential of androgen-sensitive (LNCaP) cells as well as androgen-insensitive (PC-3 and DU-145) cells. At a concentration of 200 nm, LNCaP cells showed a significant increase (20% above control; P < .0001) in cellular proliferation without any effect on androgen-insensitive cells. Furthermore, exposure to leptin caused a significant (P < .01 to P < .0001) dose-dependent decrease in migration and invasion of PC3 and Du-145 prostate carcinoma cell lines. At the molecular level, exposure of androgen-independent prostate cancer cells to leptin stimulates the phosphorylation of MAPK at early time point as well as the transcription factor STAT3, suggesting the activation of the intracellular signaling cascade upon leptin binding to its cognate receptor. Taken together, these results suggest that leptin mediates the invasive potential of prostate carcinoma cells, and that this effect is dependent on their androgen sensitivity.

Prostate cancer cell proliferation and angiogenesis in different obese mice models

“…Deo et al. has also observed that leptin also leads to STAT‐3 pathway activation in androgen dependent (DU145 and PC‐3) and independent cell lines (LNCaP) and to cellular proliferation in LNCaP cells (Deo et al. 2008).…”

“…Hoda and Popken (2008) in in vitro studies using two androgen independent human prostate cancer cell lines, DU145 and PC‐3, grown in the presence of leptin have demonstrated that leptin promotes cellular proliferation and inhibits apoptosis, while Deo et al. (2008) that studied the same two cellular lines mentioned above and also the LNCaP androgen independent cell line, has verified that leptin only enhanced the cellular growth in the last one.…”

“…In vitro studies, using human prostate cancer cells in culture, namely androgen independent DU145 and PC‐3 cell lines (Somasundar et al. 2003; Deo et al. 2008; Hoda & Popken 2008) and androgen dependent LNCaP cell line (Deo et al.…”

“…In our study, since the results obtained after immunocytochemistry for the long isoform of the leptin receptors supported the presence of OBRb in RM1 cells, and leptin levels were negatively correlated with tumour size, these results suggest that leptin is not a tumour growth factor for RM1 cells in vivo , and could even function as RM1 proliferation inhibitor. To further clarify the role of the OBR receptor in RM1 cell proliferation activated by leptin it would be pertinent to evaluate cellular growth in the presence of leptin in vitro and to study the intracellular pathways of signal activation like MAPK, STAT3 and PI3‐K similarly to what has been done with other cell lines (Deo et al. 2008; Hoda & Popken 2008).…”

Leptin increases motility and integrin up‐regulation in human prostate cancer cells

“…Previous studies have consistently shown a positive association between adiposity and increased risk of cancer of the endometrium, kidney, colon, and breast cancer in postmenopausal women (Bergstrom et al, 2001; Peto, 2001). Leptin also increases the migration of human prostate cancer cells (Frankenberry et al, 2004; Deo et al, 2008). We hypothesized that leptin may regulate migration of prostate cancer cells through the up‐regulation of integrin.…”