Co-culture of ovarian cancer stem-like cells with macrophages induced SKOV3 cells stemness via IL-8/STAT3 signaling.

Among recent concepts in the cancer biology field, the tumor microenvironment is highly associated with cancer stem cells, and plays a key role in tumor progression. This study aimed to explore the mechanism that the stemness induction of SKOV3 cell line by macrophages derived from THP-1 cells, which was co-cultured with SKOV3-derived ovarian cancer stem-like cells (OCSLCs). Sphere formation, soft agar colony formation, and expression levels of CD133 and CD44 were assessed to reflect OCSLC properties. ELISA was used to evaluate secretion profile changes in macrophages co-cultured with or without SKOV3-derived OCSLCs. For mechanistic evaluation, rhIL-8, IL-8 neutralizing antibody (IL-8 Ab), signal transducer and activator of transcription 3 (STAT3) shRNA and STAT3 cDNA were used. The results showed that IL-10, VEGF, MMP-9, IL-8 secretion and CD163 and STAT3 expression levels in macrophages co-cultured with OCSLCs were increased compared with those from THP-1 cells, while IL-12 and NO amounts were significantly reduced, reflecting M2 macrophage polarization. Addition of rhIL-8 to THP-1 cell conditioned media promoted M2 macrophage polarization and stemness in SKOV3 cells, which were suppressed by IL-8 Ab addition to co-culture conditioned media. Consistently, overexpression of STAT3 induced M2 macrophage polarization and stemness in SKOV3 cells, which were inhibited by STAT3 knockdown in macrophages from THP-1 cells. Importantly, STAT3 overexpression rescued the effects of IL-8 Ab on M2 macrophage polarization and stemness in SKOV3 cells. These results suggested that stemness induction in SKOV3 cells by macrophages co-cultured with SKOV3-derived OCSLCs involved IL-8/STAT3 signaling.

Ning Y ，Cui Y ，Li X ，Cao X ，Chen A ，Xu C ，Cao J ，Luo X ... -  《-》

Genistein inhibits stemness of SKOV3 cells induced by macrophages co-cultured with ovarian cancer stem-like cells through IL-8/STAT3 axis.

Ning Y ，Feng W ，Cao X ，Ren K ，Quan M ，Chen A ，Xu C ，Qiu Y ，Cao J ，Li X ，Luo X ... -  《-》

Involvement of M2-polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via Stat3 activation.

Ascites macrophages in advanced epithelial ovarian cancer (AdEOC) are involved in cancer metastasis and progression by modifying the tumor microenvironment. However, the precise mechanisms of cell-to-cell interaction between macrophages and tumor cells are still unclear. This study focused on the activation of signal transducer and activator of transcription 3 (Stat3) which is a critical signal transduction molecule at a point of convergence for numerous oncogenic signaling pathways as well as controlling the M2-poralization of macrophages. AdEOC ascites, in which high concentration of interleukin (IL)-6, IL-10, growth-related oncogene-alpha and vascular endothelial growth factor were detected, stimulated the proliferation of SKOV3 cells, a human ovarian cancer cell line. The simultaneous blocking of IL-6 and IL-10 by neutralizing antibodies suppressed ascites-induced tumor cell proliferation. Stat3 activation in SKOV3 cells was induced by co-culture with macrophages especially with macrophage colony stimulating factor-primed M2 macrophages but lesser extent with granulocyte-macrophage colony stimulating factor-primed immature macrophages. Cyclin-D1 expression in SKOV3 cells was also significantly induced by co-culture with macrophages. Blocking of Stat3 in macrophages by small interfering RNA inhibited the production of IL-6 and IL-10 by macrophages, and suppressed Stat3 activation and cyclin-D1 induction in co-cultured SKOV3 cells. Stat3 activation in SKOV3 cells was abrogated by simultaneous neutralization of IL-6 and IL-10. These results indicate that Stat3 activation by IL-6 and IL-10 plays an important role in cell-to-cell interaction between tumor cells and macrophages in the ascites of AdEOC.

Takaishi K ，Komohara Y ，Tashiro H ，Ohtake H ，Nakagawa T ，Katabuchi H ，Takeya M ... -  《-》

MiR-217 Inhibits M2-Like Macrophage Polarization by Suppressing Secretion of Interleukin-6 in Ovarian Cancer.

Jiang B ，Zhu SJ ，Xiao SS ，Xue M ... -  《-》

[Gastric cancer-derived mesenchymal stem cells regulate the M2 polarization of macrophages within gastric cancer microenvironment via JAK2/STAT3 signaling pathway].

Li W ，Zhao SL ，Zheng P ，Shi PQ ，Zhou Y ，Zhang T ，Huo J ，Yang J ... -  《-》