Abstract
AbstractIt is now well-established that an obese condition correlates with a higher risk of prostate cancer (PCa). A crosstalk between adipose tissue and PCa has been observed but is still poorly characterized. Herein, we demonstrated that 3T3-L1 adipocyte conditioned media (CM) could endow PC3 and DU145 PCa cells with stemness properties, by stimulating their sphere formation ability and promoting CD133 and CD44 expression. Moreover, after exposure to adipocyte CM both PCa cell lines underwent partial epithelial-to-mesenchymal transition (EMT), with E-/N-cadherin switch and Snail upregulation. Specifically, these changes in PC3 and DU145 cell phenotype were accompanied by increased tumor clonogenic activity and survival, as well as by enhanced invasion, anoikis resistance and matrix metalloproteinase (MMP) production. Finally, adipocyte CM-treated PCa cells exhibited reduced responsiveness to both docetaxel and cabazitaxel, demonstrating greater chemoresistance. Overall, these data indicate that adipose tissue can effectively contribute to PCa aggressiveness by reprogramming the cancer stem cell (CSC) machinery.
Graphical abstract
Adipocytes endow prostate cancer cells with stem-like properties and mesenchymal traits, increasing their tumorigenicity, invasion and chemoresistance.
Funder
PRIN 2015
Ministero dell’Istruzione, dell’Università e della Ricerca
Associazione Italiana per la Ricerca sul Cancro
Università degli Studi di Milano
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
2 articles.
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