Raw macrophage cell line m1 to m2 polarization
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Malignant tumors are a complex assembly of genetically heterogeneous cancer cells and different cell types that constitute the local tumor microenvironment. New therapeutic strategies are, therefore, urgently needed to delay tumor growth and to prevent metastasis. Treatment resistance and regrowth of tumors after chemo- or radiotherapy pose a major threat to the survival of cancer patients. Each year, approximately, 1.36 Mio patients are diagnosed with colorectal cancer worldwide and ∼700.000 patients die because of this malignancy. These results contribute to our understanding of the immunological mechanisms that underlie the anti-tumorigenic effects of lipids for future combination with drugs in the therapy of colorectal carcinoma.Ĭolorectal cancer is among the most prevalent cancers in both genders. Importantly, PA and Cer were powerful inhibitors of this signaling axis and, consequently, EMT of colorectal cancer cells. For the first time, our findings suggest the presence of an IL-10-STAT3-NF-κB signaling axis in colorectal cancer cells co-cultured with M2 macrophages, mimicking the tumor microenvironment. Furthermore, Cer and PA attenuated expression levels of IL-10 in colorectal cancer cells co-cultured with M2 macrophages and downregulated STAT3 and NF-κB expression. At the molecular level, this coincided with inhibition of SNAI1 and vimentin expression and upregulation of E-cadherin. Moreover, Cer and PA abolished M2 macrophage-induced EMT and migration of colorectal cancer cells. Our study showed that Cer- and PA-treated macrophages increased expression of the macrophage 1 (M1)-marker CD68 and secretion of IL-12 and attenuated expression of the macrophage 2 (M2)-marker CD163 and IL-10 secretion. The aim of the present study was to investigate whether Cer and PA could induce switching of macrophage polarization from the tumorigenic M2- towards the pro-inflammatory M1-phenotype, and whether this consequently altered the potential of colorectal cancer cells to undergo epithelial–mesenchymal transition (EMT), a hallmark of tumor progression. Accumulating evidence indicates that ceramide (Cer) and palmitic acid (PA) possess the ability to modulate switching of macrophage phenotypes and possess anti-tumorigenic effects however, the underlying molecular mechanisms are largely unknown.