Jilin Province Key Laboratory on Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, PR China.
Jilin Province Key Laboratory on Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, PR China.
Carbohydr Polym. 2019 Dec 15;226:115295. doi: 10.1016/j.carbpol.2019.115295. Epub 2019 Sep 4.
Tumor-associated macrophages (TAMs) with an M2-like phenotype have been linked to the proliferation, invasion and metastasis of tumor cells. Resetting tumor-associated macrophages represents an attractive target for an effective cancer immunotherapy. WCCP-N-b, a novel linear 3-O-methylated galactan, isolated from Cantharellus cibarius, can convert tumor-promoting M2-like macrophages to tumor-inhibiting M1-like phenotype. On a cellular mechanistic level, WCCP-N-b inhibited M2-like macrophages polarization through suppression of STAT6 activation. Furthermore, WCCP-N-b increased the phosphorylation of mitogen-activated protein kinases (MAPKs) and degradation of IκB-α through targeting Toll-like receptor 2 (TLR2). The activation of MAPKs and degradation of IκB-α were responsible for converting M2-like macrophages to M1-like macrophages. Importantly, cell culture supernatants of WCCP-N-b-treated M2-like macrophages could inhibit the cell viability of B16F1 and B16F10. Our findings provide a potential natural and harmless polysaccharide for macrophage-based tumor immunotherapy.
肿瘤相关巨噬细胞（TAMs）具有 M2 样表型，与肿瘤细胞的增殖、侵袭和转移有关。重置肿瘤相关巨噬细胞是一种有吸引力的有效癌症免疫治疗靶点。WCCP-N-b 是一种从鸡油菌中分离得到的新型线性 3-O-甲基半乳糖，可将促肿瘤的 M2 样巨噬细胞转化为抑制肿瘤的 M1 样表型。在细胞机制水平上，WCCP-N-b 通过抑制 STAT6 激活来抑制 M2 样巨噬细胞极化。此外，WCCP-N-b 通过靶向 Toll 样受体 2（TLR2）增加丝裂原活化蛋白激酶（MAPKs）的磷酸化和 IκB-α 的降解。MAPKs 的激活和 IκB-α 的降解负责将 M2 样巨噬细胞转化为 M1 样巨噬细胞。重要的是，WCCP-N-b 处理的 M2 样巨噬细胞的细胞培养上清液可抑制 B16F1 和 B16F10 的细胞活力。我们的研究结果为基于巨噬细胞的肿瘤免疫治疗提供了一种潜在的天然、无害的多糖。
