Prostate international · 2025
Interleukin-6 secreted by tumor-associated macrophages promotes proliferation and migration through JAK2/STAT3 signaling pathway in human prostate cancer cells.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Seok Eunji, Lee Dong Min, Yang Hyunwon, Yoo Tag Keun
Аннотация
BACKGROUND: 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.
MATERIALS AND METHODS: THP-1 monocytes were differentiated into M0 macrophages using phorbol 12-myristate 13-acetate 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.
RESULTS: 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.
CONCLUSIONS: 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.
MATERIALS AND METHODS: THP-1 monocytes were differentiated into M0 macrophages using phorbol 12-myristate 13-acetate 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.
RESULTS: 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.
CONCLUSIONS: 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.