title: Ovarian cancer stem-like cells elicit the polarization of M2 macrophages.
abstract: Ovarian cancer is a life‑threatening disease in females worldwide. The polarization of macrophages is crucial in oncogenesis and the development of ovarian cancer. Increasing evidence has supported the correlation between ovarian cancer stem‑like cells (OCSCs) and macrophages, however, whether OCSCs can affect the polarization of macrophages and the underlying mechanisms involved remain to be elucidated. To examine the interplay between OCSCs and macrophages, a co‑culture system was used to detect the effect of OCSCs on macrophage polarization. The expression of cluster of differentiation 206+ and the secretion of interleukin‑10 were significantly increased and the production of tumor necrosis factor‑α was suppressed, confirming macrophage polarization to M2 macrophages. Further investigation of the macrophages in a Transwell culture system with OCSCs revealed polarization to the M2 macrophages to a similar extent, indicating that the cytokines of the OCSCs, rather than direct cell‑cell contact, are important for the polarization of M2 macrophages. Furthermore, the expression levels of chemokine (C‑C motif) ligand (CCL)2, cyclooxygenase (COX)‑2 and prostaglandin E2 (PGE2) were increased in the Transwell system and the inhibition of COX‑2, but not CCL2, significantly decreased the polarization of the M2 macrophages. In addition, mechanistic analysis revealed the importance of the COX‑2/PGE2 pathway in OCSCs to activate Janus kinase (JAK) signaling in macrophages to elicit M2 polarization. These findings provided the first evidence, to the best of our knowledge, that OCSCs are capable of altering macrophages into the M2 phenotype via the overexpression of COX‑2 and the increased production of PGE2 cytokines and that the JAK signaling pathway in macrophages is important for this alteration. The present study provided evidence supporting possible molecular targets for cancer treatment.
authors: Department of Gynecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
authors: Qing
authors: Q
authors: Zhang
authors: Department of Gynecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
authors: Da-Jun
authors: DJ
authors: Cai
authors: Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors: Bin
authors: B
authors: Li
mesh_terms: D000328:Adult; D018929:Cell Culture Techniques; D016764:Cell Polarity; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D051546:Cyclooxygenase 2; D053612:Janus Kinases; D015232:Dinoprostone