M-CSF cooperating with NFκB induces macrophage transformation from M1 to M2 by upregulating c-Jun

• DOI: 10.4161/cbt.26718
• Publication Date: 2013-10-07T17:38:02Z
• Authors: Yujiao Yang; Junfang Qin; Lan Lan; Ning Li; Chengfang Wang; Pengfei He; Fang Liu; Hong Ni; Yue Wang
• Keywords: Transcriptional Activation; 0301 basic medicine; Proto-Oncogene Proteins c-jun; Macrophage Colony-Stimulating Factor; Macrophages; JNK Mitogen-Activated Protein Kinases; NF-kappa B; Coculture Techniques; 3. Good health; Transcription Factor AP-1; Mice; 03 medical and health sciences; Cell Transformation, Neoplastic; Cell Line, Tumor; Animals; Extracellular Signal-Regulated MAP Kinases; Signal Transduction

Increasing evidence suggests tumor-associated macrophages (TAMs) are polarized M2 subtype of macrophage that exerts pro-tumor effects and promote the malignancy some cancers, but concrete mechanism is not well defined. Our previous research exhibited proto-oncogene AP-1 regulated IL-6 expression in promoted formation macrophages. In this study, we investigate whether extra-cellular stimulus M-CSF help process or nuclear factor NFκB has a synergistic role activation state macrophage. RAW 264.7 4T1 mouse breast cancer cells were co-cultured to reconstruct tumor microenvironment. Being with its supernatant, c-Jun, member family, dramatically increase both on level gene protein macrophages, c-Fos does neither nor protein. After 4T1, higher consumption than alone. With stimulation M-CSF, mRNA c-Jun increased significantly, decreased remarkably after adding anti-M-CSF. And at same time, p50, similar tendency c-Jun. WB results suggest p-Jun increases heavily decreases neutralizing antibody added. Coimmunoprecipitation immunoblotting techniques confirmed p50 coprecipitated, properly enhanced rM-CSF effect. conclusion, induces transformation by upregulating certain synergy NFκB. study may present novel therapeutic strategy against cancer.