Influence of Adipocytes on Prostate Cancer Epithelial Cells

TESONE A, SACCA P , PISTONE CREYDT V, JALON M , MAZZA O , CALVO J

Shanghai, China

Congreso; 30th Congress of the Societé Internationale d Urologie; 2009

Societé Internationale d Urologie

Introduction and Objective: Adipose tissue is present in the periphery of the prostate and also at the most frequent metastatic sites. We examined the influence that soluble factors secreted by adipocytes have on parameters associated with metastasis in LNCaP (androgen dependent) and PC3 (androgen independent) PCa cell lines. Materials and Methods: We collected conditioned media (CM) of preadipocytes cell line 3T3-L1 (CMpreA1) and preadipocytes obtained from primary culture of periprostatic adipose tissue of a patient with PCa (Gleason 6, pT3aNxM0) (CMpreA2). Preadipocytes were differentiated into adipocytes and CM was also collected (CMA1 and CMA2, respectively). We incubated LNCaP and PC3 with CMpreA and CMA and analyzed cell proliferation (MTS assay), migration (wound healing) and metalloproteinases activity (MMP) (zymography). Results: CMA1 stimulated proliferation of LNCaP at 24 h and 48 h (40% and 87%, P<0.001 vs control) and the effect was stronger than CMpreA1 at the same times (P<0.01). Similarly, CMpreA2 and CMA2 promoted LNCaP proliferation at 24 h (21% and 11%, P<0.001 and P< 0.05 vs control, respectively). Incubation of PC3 with CMpreA1 and CMA1 also stimulated proliferation but only at 24 h (41% and 44%, P 0.001 vs control). Meanwhile, CMpreA2 and CMA2 stimulated proliferation after 48 h of exposure (13% and 22%, P<0.05 and P<0.001 vs control, respectively). PC3 exposure to CMA1, CMpreA2 and CMA2 resulted in an enhanced migration (42%, 33% and 46%, P0.001 vs control). Moreover, high levels of pro-MMP9 activity were detected in CM derived from PC3 cultured with CMpreA1, CMA1, CMpreA2 or CMA2 (32%, 51%, 50% and 97%, respectively, P<0.05 (CMpreA) and P<0.001 (CMA) vs control. Surprisingly, neither migration nor metalloproteases activity was observed in LNCaP with any of the CM assayed. Conclusions: Our results provide evidence that soluble factors secreted by preadipocytes at various stages of differentiation modulate several steps of the metastatic cascade in a differential manner. The differential response of both cell lines could represent either an intrinsic characteristic of the cells or reflect the different stages of the disease, starting as hormone dependent and continuing towards a hormone-independent, more adipose-responsive, metastatic fashion.