Interleukin-6 secreted by tumor-associated macrophages promotes proliferation and migration through JAK2/STAT3 signaling pathway in human prostate cancer cells

Tumor-associated macrophages (TAMs) within the tumor microenvironment secrete cytokines that promote cancer progression, proliferation, and metastasis. In prostate cancer, disease progression is closely associated with cytokine activity, particularly interleukin-6 (IL-6), which activates STAT3 to regulate cellular proliferation. Therefore, this study investigated the mechanisms by which TAM-derived IL-6 interacts with prostate cancer cells to affect cancer cell proliferation and metastasis. THP-1 monocytes were differentiated into M0 macrophages using phorbol 12-myristate 13-acetate (PMA) and subsequently co-cultured with conditioned medium (CM) from PC3 prostate cancer cells to induce TAM polarization. Cytokine secretion from TAMs was analyzed using qRT-PCR and cytokine arrays. PC3 cell proliferation, invasion, and migration were evaluated using MTT, Transwell invasion, and wound-healing assays, respectively. The expression of proliferation-related genes, including TGF-α, TGF-β1, mTOR, FOS, CCND1, and PXN , was assessed using qRT-PCR. The effect of IL-6 on JAK2/STAT3 signaling was examined using Western blotting. CM from PC3 cells induced TAM polarization and significantly increased IL-6 expression in TAMs. TAMs enhanced the proliferation, invasion, and migration of PC3 cells, but these effects were suppressed by the STAT3 inhibitor WP1066 and IL-6 neutralizing antibodies. Furthermore, TGF-α and FOS expression was increased in PC3 cells co-cultured with TAMs, but this increase was reduced by WP1066 and IL-6 neutralizing antibody. IL-6 increased the activation of JAK2 and STAT3 proteins in PC3 cells, which was reduced by both treatments. These findings underscore the role of TAMs in promoting prostate cancer progression through IL-6-mediated JAK2/STAT3 signaling, suggesting the potential of targeting this pathway as a therapeutic strategy for advanced prostate cancer.