Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro
1 Molecular Oncology Group-CI, Portuguese Institute of Oncology, Porto, Portugal
2 Abel Salazar Biomedical Sciences Institute, University of Porto, Porto, Portugal
3 Research Department-Portuguese League Against Cancer (NRNorte), LPCC, Porto, Portugal
4 Biomaterials Division, NEWTherapies Group, INEB, Porto, Portugal
5 Department of Pathology and Oncology, Faculty of Medicine, Porto, Portugal
6 General Pathology Laboratory, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
7 CIMAGO, Centre of Investigation in Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
8 CNC, Centre of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal
9 Urology Department, Porto Hospital Centre, Porto, Portugal
10 Urology Department, Porto Military Hospital, Porto, Portugal
11 Urology Department, Portuguese Institute of Oncology, Porto, Portugal
12 Urology Department, S. João Hospital, Porto, Portugal
13 Molecular Oncology Group - CI, Portuguese Institute of Oncology, Porto Centre, Edifício Laboratórios - Piso 4, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal
Journal of Experimental & Clinical Cancer Research 2012, 31:32 doi:10.1186/1756-9966-31-32Published: 2 April 2012
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.
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.
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.
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.