Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro

Journal of Experimental & Clinical Cancer Research

Rui Medeiros⁶  Carlos Lopes¹  Anabela Mota-Pinto²  Francisco Pina⁹  Jorge Oliveira³  José Sanches-Magalhães³  Vítor Silva³  António Morais³  Francisco Lobo³  Carlos Lobato⁸  Paulo Príncipe⁵  Avelino Fraga⁵  Mariana Freitas⁷  Maria José Oliveira⁴  Virgínia Cunha⁶  Cátia Monteiro⁶  Ricardo Ribeiro⁶ 

[1] Abel Salazar Biomedical Sciences Institute, University of Porto, Porto, Portugal;CIMAGO, Centre of Investigation in Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal;Urology Department, Portuguese Institute of Oncology, Porto, Portugal;Department of Pathology and Oncology, Faculty of Medicine, Porto, Portugal;Urology Department, Porto Hospital Centre, Porto, Portugal;Research Department-Portuguese League Against Cancer (NRNorte), LPCC, Porto, Portugal;CNC, Centre of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal;Urology Department, Porto Military Hospital, Porto, Portugal;Urology Department, S. João Hospital, Porto, Portugal

关键词: Prostate cancer;    Periprostatic;    Obesity;    Cell tracking;    Cell proliferation;    Cell line;    Adipose tissue;   

Others  :  826652
DOI  :  10.1186/1756-9966-31-32

 received in 2012-02-23, accepted in 2012-04-02,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Ribeiro et al; licensee BioMed Central Ltd.

【 图 表 】

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