Co-culture of ovarian cancer stem-like cells with macrophages induced SKOV3 cells stemness via IL-8/STAT3 signaling - 29/05/18
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Graphical abstract |
Highlights |
• | co-culture with OCSLCs activated THP-1 macrophages to M2 phenotype polarization. |
• | Co-culture of OCSLCs and THP-1 macrophages promoted the stemness of SKOV3 cells. |
• | IL-8/STAT3 signaling involved in the interation of OCSLC and THP-1 macrophage. |
Abstract |
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.
El texto completo de este artículo está disponible en PDF.Abbreviations : CSC, SFC, OCSC, OCSLC, TME, ECM, TAM, CM, OCSLC-CM, THP-1-CM, Co-CM
Keywords : Cancer-associated macrophage, Cancer stem cell, IL-8, Ovarian cancer, Signal transducer and activator of transcription 3
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Vol 103
P. 262-271 - juillet 2018 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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