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Title: Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro
Authors: Ribeiro, Ricardo 
Monteiro, Cátia 
Cunha, Virgínia 
Oliveira, Maria José 
Freitas, Mariana 
Fraga, Avelino 
Príncipe, Paulo 
Lobato, Carlos 
Lobo, Francisco 
Morais, António 
Silva, Vítor 
Sanches-Magalhães, José 
Oliveira, Jorge 
Pina, Francisco 
Mota-Pinto, Anabela 
Lopes, Carlos 
Medeiros, Rui 
Keywords: Prostate cancer; Adipose tissue; Cell line; Cell proliferation; Cell tracking
Issue Date: 2-Apr-2012
Publisher: BioMed Central Ltd
Citation: RIBEIRO, Ricardo [et. al.] - Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro. "Journal of Experimental and Clinical Cancer Research". ISSN 0392-9078. 31:1 (2012) 32
Serial title, monograph or event: Journal of Experimental and Clinical Cancer Research
Volume: 31
Issue: 1
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.
DOI: 10.1186/1756-9966-31-32
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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