title: Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro.
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.
authors.affiliation: Molecular Oncology Group-CI, Portuguese Institute of Oncology, Porto, Portugal. oriebir.r@gmail.com
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ribeiro
authors.forename: Cátia
authors.initials: C
authors.lastname: Monteiro
authors.forename: Virgínia
authors.initials: V
authors.lastname: Cunha
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Oliveira
authors.forename: Mariana
authors.initials: M
authors.lastname: Freitas
authors.forename: Avelino
authors.initials: A
authors.lastname: Fraga
authors.forename: Paulo
authors.initials: P
authors.lastname: Príncipe
authors.forename: Carlos
authors.initials: C
authors.lastname: Lobato
authors.forename: Francisco
authors.initials: F
authors.lastname: Lobo
authors.forename: António
authors.initials: A
authors.lastname: Morais
authors.forename: Vítor
authors.initials: V
authors.lastname: Silva
authors.forename: José
authors.initials: J
authors.lastname: Sanches-Magalhães
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.forename: Francisco
authors.initials: F
authors.lastname: Pina
authors.forename: Anabela
authors.initials: A
authors.lastname: Mota-Pinto
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology / Q000473:pathology*; D000368:Aged; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009765:Obesity / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*
chemical_list: D017077:Culture Media, Conditioned; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9