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.

Three‐dimensional cell culture model utilization in cancer stem cell research

“…The impact of stromal cell components on the tumor microenvironment was described in several studies (Bezdenezhnykh et al , ; Wan et al , ; Zhang, Cai & Li, ). It is known that since the molecular composition of the microenvironment of the tumor is formed not only by cancer cells and CSCs and their metabolic products, but also by resident/infiltrating non‐tumor cells, inter‐ and intracellular interactions may be difficult to recapitulate in in vitro conditions.…”

Signal regulatory protein α associated with the progression of oral leukoplakia and oral squamous cell carcinoma regulates phenotype switch of macrophages

“…Various studies have indicated that inhibition of NF-κB activation helps to drive the tumor-promoting phenotype of TAMs [12, 13]. Macrophages are polarized to M2-like phenotype by malignant epithelial cells [14]. Positive correlation was found between macrophage infiltrated in the tumor stroma and OSCC with a higher histological grading [15].…”

Platinum sensitivity of ovarian cancer cells does not influence their ability to induce M2‐type macrophage polarization

“…Indeed, ovarian cancer or stem-like cancer cells were previously reported to polarize macrophages into M2 phenotype. [58][59][60] Therefore, we suggest that ovarian cancer cells tend to induce M2-like mRNA profile independent of their platinum sensitivity status. However, we examined only one ovarian cancer cell line and its derivatives, hence avoiding the possible impact of variation between different cell lines.…”