Extracellular Vesicles Released From Prostate Cancer Cells Confer Pro-Tumor Properties to Adipocytes by Stimulating...

Area of Science:

• Oncology
• Cell Biology
• Metabolism

Background:

• Obesity is linked to increased prostate cancer (PCa) risk.
• Communication between PCa cells and adipocytes is known, but the role of extracellular vesicles (EVs) is unclear.

Purpose of the Study:

• To investigate the role of PCa-derived EVs in adipocyte function and their impact on PCa progression.

Main Methods:

• PCa EVs were used to treat 3T3-L1 adipose cells.
• Changes in lipolysis markers (G0S2, ATGL, cAMP/PKA/HSL pathway) were analyzed.
• Effects of released free fatty acids (FFAs) on PCa cell proliferation, clonogenicity, migration, invasion, and anoikis were assessed.
• Akt activation and the effect of BEZ235 were investigated.

Main Results:

• PCa EVs induced lipolysis in adipocytes by downregulating G0S2 and upregulating ATGL, activating the cAMP/PKA/HSL pathway.
• Released FFAs enhanced PCa cell proliferation, clonogenicity, migration, and invasion while reducing anoikis.
• FFAs promoted PCa progression via Akt activation, which was inhibited by BEZ235.

Conclusions:

• PCa EVs mediate a bidirectional communication with adipocytes.
• This interaction reprograms adipocytes into a lipolytic, tumor-promoting phenotype, contributing to obesity-associated PCa progression.