BACKGROUND: The @entity5 microenvironment plays in an important role in the progression of @entity5 by mediating stromal-epithelial paracrine signaling, which can aberrantly modulate cellular proliferation and tumorigenesis. Exposure to environmental toxicants, such as inorganic @entity3494 (iAs), has also been implicated in the progression of @entity263 . OBJECTIVE: The role of iAs exposure on stromal signaling in the @entity5 microenvironment largely has been unexplored. Our objective was to elucidate molecular mechanisms of iAs-induced changes to stromal signaling by an enriched @entity263 microenvironment cell population, adipose-derived mesenchymal stem/stromal cells (ASC). RESULTS: ASC conditioned media (CM) collected after one week of iAs exposure @entity263 cell viability compared to ASC CM which received no iAs exposure. Cytokine array analysis suggested changes to cytokine signaling associated with iAs exposure. Subsequent proteomic analysis suggested a concentration-dependent alteration to the @entity13975 / @entity3499 / @entity2533 signaling pathway by iAs. These results were validated by quantitative RT-PCR and Western blot, confirming a concentration-dependent increase in @entity13975 and decrease in @entity3499 expression in ASC following iAs exposure. Subsequently, utilizing a @entity2533 pathway reporter construct we confirmed a decrease in stromal @entity2533 signaling in ASC following iAs exposure. CONCLUSIONS: Our results suggest a concentration-dependent alteration of stromal signaling, specifically attenuation of stromal-mediated @entity2533 signaling following exposure to iAs. Our results indicate iAs may enhance @entity263 cell viability through a previously unreported stromal-based mechanism. These findings illustrate that the stroma may mediate the effects of iAs in @entity5 progression, which may have future therapeutic implications.

Inorganic @entity3494 Related Changes in the @entity5 Microenvironment in a XXXX Cell-Conditioned Media Model.

@entity3499 :: ('7057', 'Gene') :: ['THBS1'] @entity263 :: ('MESH:D011471', 'Disease') :: ['prostate cancer', 'prostate tumor', 'increased prostate cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity2533 :: ('7040', 'Gene') :: ['TGFb'] @entity13975 :: ('3162', 'Gene') :: ['HMOX1'] @entity3494 :: ('MESH:D001151', 'Chemical') :: ['arsenic']
@entity263 :: (MESH:D011471,Disease) :: ['Prostate Cancer']
