Lipolysis-stimulated lipoprotein receptor is involved in fatty acid binding protein 4-mediated prostate cancer cell growth in bone

Obesity-induced excess adipokine production is associated with malignancy and mortality in prostate cancer. We previously showed that fatty acid binding protein 4 (FABP4), a major adipokine of mature adipocytes, promotes the progression of prostate cancer cell growth and invasion. In this report, we present lipolysis-stimulated lipoprotein receptor (LSR) as a newly identified binding partner for FABP4. Their binding induced Akt phosphorylation, whereas LSR knockdown (KD) failed to phosphorylate Akt. Intraosseous injection of LSR-KD prostate cancer cells showed smaller areas of intraosseous tumor, lower Ki-67 labeling indices, and lower numbers of phospho-Akt-positive cancer cells compared with control prostate cancer cells. Moreover, the contact coculture of prostate cancer cells with bone marrow stromal cells (BMSCs) promoted FABP4 secretion by BMSCs. Our findings indicated that FABP4-mediated prostate cancer cell progression was regulated by cellular signaling via FABP4-LSR binding in the bone microenvironment. J. Med. Invest. 72 : 34-41, February, 2025.