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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2012 | Research

Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro

Authors: Ricardo Ribeiro, Cátia Monteiro, Virgínia Cunha, Maria José Oliveira, Mariana Freitas, Avelino Fraga, Paulo Príncipe, Carlos Lobato, Francisco Lobo, António Morais, Vítor Silva, José Sanches-Magalhães, Jorge Oliveira, Francisco Pina, Anabela Mota-Pinto, Carlos Lopes, Rui Medeiros

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2012

Abstract

Background

Obesity is associated with prostate cancer aggressiveness and mortality. The contribution of periprostatic adipose tissue, which is often infiltrated by malignant cells, to cancer progression is largely unknown. Thus, this study aimed to determine if periprostatic adipose tissue is linked with aggressive tumor biology in prostate cancer.

Methods

Supernatants of whole adipose tissue (explants) or stromal vascular fraction (SVF) from paired fat samples of periprostatic (PP) and pre-peritoneal visceral (VIS) anatomic origin from different donors were prepared and analyzed for matrix metalloproteinases (MMPs) 2 and 9 activity. The effects of those conditioned media (CM) on growth and migration of hormone-refractory (PC-3) and hormone-sensitive (LNCaP) prostate cancer cells were measured.

Results

We show here that PP adipose tissue of overweight men has higher MMP9 activity in comparison with normal subjects. The observed increased activities of both MMP2 and MMP9 in PP whole adipose tissue explants, likely reveal the contribution of adipocytes plus stromal-vascular fraction (SVF) as opposed to SVF alone. MMP2 activity was higher for PP when compared to VIS adipose tissue. When PC-3 cells were stimulated with CM from PP adipose tissue explants, increased proliferative and migratory capacities were observed, but not in the presence of SVF. Conversely, when LNCaP cells were stimulated with PP explants CM, we found enhanced motility despite the inhibition of proliferation, whereas CM derived from SVF increased both cell proliferation and motility. Explants culture and using adipose tissue of PP origin are most effective in promoting proliferation and migration of PC-3 cells, as respectively compared with SVF culture and using adipose tissue of VIS origin. In LNCaP cells, while explants CM cause increased migration compared to SVF, the use of PP adipose tissue to generate CM result in the increase of both cellular proliferation and migration.

Conclusions

Our findings suggest that the PP depot has the potential to modulate extra-prostatic tumor cells' microenvironment through increased MMPs activity and to promote prostate cancer cell survival and migration. Adipocyte-derived factors likely have a relevant proliferative and motile role.

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Title: Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro
Authors: Ricardo Ribeiro
Cátia Monteiro
Virgínia Cunha
Maria José Oliveira
Mariana Freitas
Avelino Fraga
Paulo Príncipe
Carlos Lobato
Francisco Lobo
António Morais
Vítor Silva
José Sanches-Magalhães
Jorge Oliveira
Francisco Pina
Anabela Mota-Pinto
Carlos Lopes
Rui Medeiros
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2012
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/1756-9966-31-32

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