title: Immune function, mitogenicity, and angiogenic growth factor concentrations in lean and obese rodent sera: implications in obesity-related prostate tumor biology.
abstract: Some studies suggest that several tumors have a greater incidence in those patients with a high fat diet, such as colon, breast, and prostate. However, we wanted to determine the effects of obesity alone, independent of diet, on the progression of prostate tumor growth. Using a genetic model of obese and lean Zucker rats, we wanted to demonstrate any sera differences in the concentration of basic fibroblast growth factor (FGF-2) and vascular endothelial cell growth factor (VEGF), two important factors involved in the growth and progression of prostate cancer. We also wanted to investigate if there were any differences in immune function between the two sera, which could also account for uninhibited tumor growth, as well as differences in mitogenic stimulation. Female Zucker rat obese and lean sera were analyzed using ELISA assays for FGF-2, VEGF, and macrophage inflammatory protein-1 alpha (MIP-1a), as a measure of macrophage function. In addition, the sera of lean and obese sera were plated on wells growing LNCaP prostate cancer cells to determine differences in mitogenicity. We found a greater concentration of FGF-2 in the sera from obese Zucker rats compared to lean Zucker rats: 6.32+/-0.56 vs 3.48+/-0.34 pg/ml, respectively, P<0.05). We also demonstrated a greater concentration of VEGF in obese rat sera compared to lean sera: 54.4+/-4.1 vs 38.0+/-2.9 pg/mL, respectively, P<0.05). We detected a trend in mitogenic stimulation among LNCaP cells along the higher concentrations of the dose-response curve (0.72+/-0.06 vs 0.51+/-0.5). However, this was not statistically significant. In addition, we did not find a significant difference in MIP-1a macrophage activity levels between sera. To conclude, we speculate that the greater concentrations of VEGF and FGF-2 in the sera of obese rodents vs lean rodents may account for some of the differences seen in obesity-related tumor growth seen in the human condition. However, the lack of any sera differences of immune function, as measured by macrophage activity, as well as no significant differences on mitogenic proliferation on LNCaP prostate cancer cells, suggests that other mechanisms may exist to explain differences seen in obesity-related prostate tumor biology.
authors.affiliation: Department of Urology, Temple University School of Medicine, Philadelphia Pennsylvania 19140, USA. jmydlo@astro.temple.edu
authors.forename: J H
authors.initials: JH
authors.lastname: Mydlo
authors.forename: M I
authors.initials: MI
authors.lastname: Gerstein
authors.forename: C F
authors.initials: CF
authors.lastname: Harris
authors.forename: A S
authors.initials: AS
authors.lastname: Braverman
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000097:blood*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D054407:Chemokine CCL4; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000473:pathology*; D051381:Rats; D011924:Rats, Zucker; D044005:Tetrahydroisoquinolines / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D043925:Angiogenesis Inducing Agents; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D008934:Mitogens; D044005:Tetrahydroisoquinolines; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D016222:Fibroblast Growth Factor 2; C058571:soquinolol