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Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro

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11 pages
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.
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Ribeiroet al.Journal of Experimental & Clinical Cancer Research2012,31:32 http://www.jeccr.com/content/31/1/32
R E S E A R C HOpen Access Human periprostatic adipose tissue promotes prostate cancer aggressivenessin vitro 1,2,3,13* 1,3 1,34,5 6,7,89 Ricardo Ribeiro, Cátia Monteiro, Virgínia Cunha, Maria José Oliveira, Mariana Freitas, Avelino Fraga , 9 1011 1111 11 Paulo Príncipe , Carlos Lobato, Francisco Lobo, António Morais, Vítor Silva, José SanchesMagalhães, 11 126,7 21,2,3 Jorge Oliveira, Francisco Pina, Anabela MotaPinto, Carlos Lopesand Rui Medeiros
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 cellsmicroenvironment through increased MMPs activity and to promote prostate cancer cell survival and migration. Adipocytederived factors likely have a relevant proliferative and motile role. Keywords:Adipose tissue, Cell line, Cell proliferation, Cell tracking, Obesity, Periprostatic, Prostate cancer
Background In recent years substantial evidence has been provided for the linkage between adipose tissue dysfunction and cancer progression [1,2]. Excess accumulation of adipose tissue corresponds by definition to obesity, which has been associated with prostate cancer aggressiveness [3,4].
* Correspondence: oriebir.r@gmail.com 1 Molecular Oncology GroupCI, Portuguese Institute of Oncology, Porto, Portugal Full list of author information is available at the end of the article
In prostate cancer, the extracapsular extension of can cer cells into the periprostatic (PP) fat is a pathological factor related with worst prognosis [5]. It is now well established that the interactions between nontumor cells in the microenvironment and the tumor cells are decisive of whether cancer cells progress towards metastasis or whether they remain dormant [6]. Prostate cancer cells generated within prostatic acini frequently infiltrate and even surpass the prostatic cap sule, therefore interacting with the surrounding PP
© 2012 Ribeiro et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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