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

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Abstract

Increasing evidence suggests tumor-associated macrophages (TAMs) are polarized M2 subtype of macrophage that exerts pro-tumor effects and promote the malignancy of some cancers, but the concrete mechanism is not well defined. Our previous research exhibited that proto-oncogene AP-1 regulated IL-6 expression in macrophages and promoted the formation of M2 macrophages. In this study, we investigate whether extra-cellular stimulus M-CS F help this process or nuclear factor NFκB has a synergistic role in the activation state of polarized M2 subtype of macrophage. RAW 264.7 macrophage and 4T1 mouse breast cancer cells were co-cultured to reconstruct tumor microenvironment. Being co-cultured with 4T1 or its supernatant, the expression of c-Jun, the member of AP-1 family, has a dramatically increase both on the level of gene and on the protein in RAW 264.7 macrophages, but the expression of c-Fos does not increase neither on the level of gene nor on the protein. After co-cultured with 4T1, RAW 264.7 has a higher consumption of M-CS F than RAW 264.7 macrophages alone. With the stimulation of M-CS F, the mRNA of c-Jun increased significantly, but decreased remarkably after adding the anti-M-CS F. And at the same time, p50, the member of NFκB family, has a similar tendency to c-Jun. WB results suggest that with the stimulation of M-CS F, p-Jun in nuclear increases heavily but decreases after the neutralizing antibody added. Coimmunoprecipitation and immunoblotting techniques confirmed that c-Jun and p50 NFκB coprecipitated, and c-Jun protein expression is properly enhanced with rM-CS F effect. In conclusion, M-CS F induces macrophage transformation by upregulating c-Jun with a certain synergy of NFκB. Our study may present a novel therapeutic strategy against cancer. © 2014 Landes Bioscience.

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Yang, Y., Qin, J., Lan, L., Li, N., Wang, C., He, P., … Wang, Y. (2014). M-CSF cooperating with NFκB induces macrophage transformation from M1 to M2 by upregulating c-Jun. Cancer Biology and Therapy, 15(1), 99–107. https://doi.org/10.4161/cbt.26718

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