Apoptotic SKOV3 cells stimulate M0 macrophages to differentiate into M2 macrophages and promote the�proliferation and migration of ovarian cancer�cells by activating the ERK signaling pathway

Abstract

Ovarian cancer has a high rate of recurrence, with M2 macrophages having been found to be involved in its progression and metastasis. To examine the relationship between macrophages and ovarian cancer in the present study, M0 macrophages were stimulated with apoptotic SKOV3 cells and it was found that these macrophages promoted tumor proliferation and migration. Subsequently, the mRNAs and proteins expressed at high levels in these M2 macrophages were examined by RNA-Seq and quantitative proteomics, respectively, which revealed that M0 macrophages stimulated by apoptotic SKOV3 cells also expressed M2 markers, including CD206, interleukin-10, C-C motif chemokine ligand 22, aminopeptidase-N, disabled homolog 2, matrix metalloproteinase 1 and 5′-nucleotidase. The abundance of phosphorylated Erk1/2 in these macrophages was increased. The results indicate that apoptotic SKOV3 cells stimulate M0 macrophages to differentiate into M2 macrophages by activating the ERK pathway. These results suggest possible treatments for patients with ovarian cancer who undergo chemotherapy; inhibiting M2 macrophage differentiation during chemotherapy may reduce the rate of tumor recurrence.

microRNA-18a from M2 Macrophages Inhibits TGFBR3 to Promote Nasopharyngeal Carcinoma Progression and Tumor Growth via TGF-β Signaling Pathway

“…The medium was renewed in half every 3 days and then supplemented with 100 ng/mL M-CSF. Cultivated to the 7-8th day, part of cells were harvested, and macrophage surface markers CD68 [16], CD163 [17], and CD206 [18] were tested by immunofluorescence assay [19] to identify macrophages.…”

Prognostic Value of the Intratumoral Lymphocyte to Monocyte Ratio and M0 Macrophage Enrichment in the Melanoma Immune Microenvironment

“…In ovarian cancer and glioblastoma, transcriptomic profiling demonstrated that M0 macrophages do not fit into the canonical M1 or M2 model, but M0 macrophages did have high expression of M2 markers, and a transcriptional profile more similar to M2 macropha ges [47,48]. Ultimately, M0s…”

“…may represent another type of TAM or an incompletely differentiated M2 [47]. M0 macrophages were found to be one of the cell subsets most strongly associated with poor outcome in breast cancer [49], prostate cancer [50], and lung adenocarcinoma [51], while reduced M0 content has been associated with better prognosis in bladder cancer [52].…”

Tumor-derived Exosomes Induced M2 Macrophage Polarization and Promoted the Metastasis of Osteosarcoma Cells Through Tim-3

“…In liver cancer, M2-type macrophages could promote the malignant transformation and progression of liver cancer, through the induction of expression of vascular endothelial factors and matrix metalloproteins in the TME in comparison with M1-type macrophages, and facilitate the invasion and metastasis of liver cancer, which are important factors for poor prognosis of patients with liver cancer [33]. The tumor-supporting functions of TAMs have been demonstrated for in many types of malignancies including ovarian cancer, nasopharyngeal cancer, and melanoma, TAM was dominated mostly by M2-type macrophages; however, the reprogramming of M2 macrophages towards M1 phenotype exhibited a marked negative impact on tumor progression and prognosis [7,38,39]. These pieces of evidence thus indicated that M1-type macrophages present an inhibitory effect on tumor immunity, while M2-type macrophages exhibit a tumor-supporting function including tumor invasion and metastasis.…”