Adipocytes reprogram prostate cancer stem cell machinery

It 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.

Automated summary

It has been found that obesity is associated with a higher risk of prostate cancer. The interaction between adipose tissue and prostate cancer is not fully understood. This study showed that adipocyte conditioned media can induce stemness properties in prostate cancer cells and promote certain gene expressions. Furthermore, exposure to adipocyte conditioned media led to partial epithelial-to-mesenchymal transition in the cancer cells, resulting in enhanced tumor aggressiveness and chemoresistance.