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Prostate cancer cell proliferation and angiogenesis in different obese mice models
Author(s) -
Ribeiro Andreia M.,
Andrade Sara,
Pinho Filipa,
Duarte Monteiro J.,
Costa Madalena,
Lopes Carlos,
Aguas Artur P.,
Monteiro Mariana P.
Publication year - 2010
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.1365-2613.2010.00726.x
Subject(s) - leptin , endocrinology , medicine , angiogenesis , prostate cancer , mitotic index , prostate , cell growth , testosterone (patch) , obesity , biology , cancer , mitosis , genetics , microbiology and biotechnology
Summary Obesity has been associated with increased incidence and aggressiveness of prostate cancer. Although controversial, several studies suggest that leptin could influence tumour cell growth and proliferation. The main goal of this study was to assess cellular growth of prostate adenocarcinoma cells in obese mice with different endogenous hormonal environments in what relates to leptin circulating levels and sensitivity. Four groups of mice ( n = 6/group) were used, namely obese mice with congenital non‐functioning leptin receptor OBR ( db/db ), obese mice with congenital leptin deficiency ( ob/ob ), mice with diet induced obesity (DIO) and normal weight C57BL/6J mice (control). All groups of mice were injected subcutaneously with 3.0 × 10 5 RM1 cells/500 μl PBS (murine prostate carcinoma androgen insensitive cells) and tumour growth and angiogenesis were evaluated 14 days after inoculation. The tumours induced in ob/ob and DIO mice were significantly larger ( P < 0.001) while those induced in db/db mice were significantly smaller ( P = 0.047), when compared with controls. Morphometric analysis revealed that mitotic index and Ki‐67 positive nuclear density, both cell proliferation markers, were also significantly lower in the tumours of db/db mice ( P < 0.001) when compared to controls. An inverse correlation was observed between leptin plasma levels and tumour weight ( r = −0.642, P < 0.001), mitotic index ( r = −0.646, P < 0.01) and Ki‐67 positive nuclear density ( r = −0.795, P < 0.001). These results suggest that high leptin concentrations are not favourable to RM1 cell growth and proliferation. On the contrary, high plasma leptin levels were associated with less cellular proliferation and angiogenesis in vivo .