Human Periprostatic Adipose Tissue Promotes Prostate Cancer Aggressiveness in Vitro

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2012 Apr 4

PMID 22469146

Citations 78

Authors

Ricardo Ribeiro

Catia Monteiro

Virginia Cunha

Maria Jose Oliveira

Mariana Freitas

Avelino Fraga

Paulo Principe

Carlos Lobato

Francisco Lobo

Antonio Morais

Vitor Silva

Jose Sanches-Magalhaes

Jorge Oliveira

Francisco Pina

Anabela Mota-Pinto

Carlos Lopes

Rui Medeiros

Affiliations

Soon will be listed here.

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.

Citing Articles

Periprostatic Adipose Tissue as a Contributor to Prostate Cancer Pathogenesis: A Narrative Review.

Drewa J, Lazar-Juszczak K, Adamowicz J, Juszczak K Cancers (Basel). 2025; 17(3).

PMID: 39941741 PMC: 11816168. DOI: 10.3390/cancers17030372.

Imaging of prostate micro-architecture using three-dimensional wide-field optical coherence tomography.

Skrok M, Tamborski S, Hepburn M, Fang Q, Maniewski M, Zdrenka M Biomed Opt Express. 2024; 15(12):6816-6833.

PMID: 39679405 PMC: 11640564. DOI: 10.1364/BOE.537783.

Periprostatic fat magnetic resonance imaging based radiomics nomogram for predicting biochemical recurrence-free survival in patients with non-metastatic prostate cancer after radical prostatectomy.

Wu X, Ke Z, Chen Z, Liu W, Xue Y, Chen S BMC Cancer. 2024; 24(1):1459.

PMID: 39604917 PMC: 11600801. DOI: 10.1186/s12885-024-13207-4.

MRI-measured periprostatic to subcutaneous adipose tissue thickness ratio as an independent risk factor in prostate cancer patients undergoing radical prostatectomy.

Jiang S, Li Y, Guo Y, Gong B, Wei C, Liu W Sci Rep. 2024; 14(1):20896.

PMID: 39245685 PMC: 11381511. DOI: 10.1038/s41598-024-71862-w.

Periprostatic adipose tissue inhibits tumor progression by secreting apoptotic factors: A natural barrier induced by the immune response during the early stages of prostate cancer.

Shao I, Chang T, Chang Y, Hsieh Y, Sheng T, Wang L Oncol Lett. 2024; 28(4):485.

PMID: 39170882 PMC: 11338243. DOI: 10.3892/ol.2024.14617.

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