Obesity inhibits lymphangiogenesis in prostate tumors

Abstract

Lymphangiogenesis is the process that leads to new lymphatic vessels formation from preexisting blood vessels in the presence of appropriate inducing signals, which in pathologic conditions such as cancer, may contribute to tumor cells dissemination. The aim of the present study was to study the role of obesity, leptin and insulin in tumor lymphangiogenesis. For that, we have quantified the lymphatic vessels in prostate tumors through their immunohistochemistry staining by Lyve-1 in RM1 prostate tumors induced in different obese mice models (ob/ob, db/db and diet induced obese (DIO) and in normal weight C57BL/6J mice (control). Lymph vessels density was determined by Lyve-1 immunohistochemistry of prostate adenocarcinomas, while the percentage of the Lyve-1 stained area and lymphatic vessels number were obtained using a morphometric computerized tool. Obese ob/ob and DIO mice presented prostate tumors that were significantly larger (p<0.001) than controls, while tumors of db/db mice were significantly smaller (p=0.047). Lyve-1 expression was significantly higher in prostate tumors of DIO mice compared to tumors of db/db mice (p<0.05); furthermore Lyve-1 expression was negatively correlated with the percentage of the epididymal fat and body weight (p<0.01). No significantly correlations were found between Lyve-1 expression and tumor weight and leptin or insulin plasma levels. Our results suggest that obesity may have a protective effect against prostate cancer dissemination by inhibiting lymphangiogenesis through a still unidentified mechanism that appears not to involve leptin or insulin.

Keywords: Lymphangiogenesis; leptin; obesity; prostate cancer.

Figure 1

RM1 cell prostate adenocarcinoma with lymphatic vessels stained by immunohistochemistry using anti-Lyve-1 antibody. In the micrograph, unstained blood vessels can be visualized as indicated by the dark arrows (200x) in contrast to the DAB stained lymphatic vessels.

Figure 2

Percentage of Lyve-1 stained area (A) and number of vessels marked for LYVE-1 antibody per tumor area (B) in the RM1 cell induced prostate carcinomas.