胶原蛋白具有促进肿瘤相关巨噬细胞向M1型极化的作用  

Collagen promoting macrophage polarization into M1 inflammatory phenotype

作　　者：苏小薇 吴波[1] 孙海梅[1] 杜雅兰 周德山[1] 季凤清[1] SU Xiao-wei;WU Bo;SUN Hai-mei;DU Ya-lan;ZHOU De-shan;JI Feng-qing(Department of Histology and Embryology, School of Basic Medical Sciences,Capital Medical University y Beijing 100069, China)

机构地区：[1]首都医科大学基础医学院组织学与胚胎学教研室

出　　处：《解剖学报》2019年第4期445-450,共6页Acta Anatomica Sinica

基　　金：北京市自然科学基金(5182005,5172008)

摘　　要：目的以临床结直肠肿瘤患者标本和原位癌小鼠模型以及小鼠腹腔巨噬细胞为研究对象,探讨结直肠肿瘤微环境中胶原蛋白促进肿瘤相关巨噬细胞极化的作用。方法应用免疫荧光染色检测结直肠癌患者肿瘤组织巨噬细胞的分布,检测原位癌模型小鼠肿瘤组织巨噬细胞的量和分布;Masson染色肿瘤组织内胶原纤维。提取小鼠腹腔巨噬细胞,接种于不同浓度Ⅰ型胶原蛋白包被的培养皿,Real-time PCR检测巨噬细胞的肿瘤坏死因子(TNF)、诱导型一氧化氮合酶(i NOS)、CD163、CD206等基因表达。结果人结肠癌组织标本和小鼠原位癌模型可见巨噬细胞主要分布于肿瘤组织的间质,主要为M1型,肿瘤实质部分巨噬细胞主要为M2型;细胞实验表明,胶原蛋白明显促进巨噬细胞向促进炎症抑制肿瘤的M1型巨噬细胞极化,抑制巨噬细胞向促进肿瘤的M2型极化;Masson染色可见间质内含有大量胶原纤维,而肿瘤实质细胞周围胶原纤维较少。结论胶原蛋白具有促进巨噬细胞向M1型极化的作用,而肿瘤实质细胞周围胶原纤维减少,可能与巨噬细胞向M2型极化,发挥促进肿瘤发生发展的作用有关。Objective To investigate the effect of collagen on M1 macrophage polarization in vivo and in vitro study. Methods Immunofluorescence was used to detect the distribution of macrophages in clinical colorectal tumor,and the distribution of macrophages in orthotopic carcinoma model mice. Masson staining was used to detect collagen fibers in tumor tissues. The mouse peritoneal macrophages were cultured on the cell culture dish coated by different concentration of type Ⅰ collagen,then determine the gene expression of tumor necrosis factor(TNF),inducible nitric oxide synthase(i NOS),CD163,CD206 by using Real-time PCR method. Results Macrophages were mainly distributed in the stroma of tumor tissue in human colon cancer tissue and mouse carcinoma samples,tumor-associated macrophages there were mainly M1-type,while macrophages in the parenchymal area of tumor tissue were mainly M2 macrophages;Type Ⅰ collagen induces macrophages polarization into M1 phenotype and inhibits the macrophages to the tumor-promoting M2-type in vitro;Masson staining showed that collagen fibers were mainly distributed in the stroma of tumor tissue both in human and mouse tumor,and collagen fibers around the tumor parenchymal cells were less,however,collagen fibers were abundant in the stroma of tumor tissue. Conclusion Type Ⅰ collagen induces the polarization of macrophages to M1 phenotype,while the decrease of collagen fibers around the tumor parenchymal cells may be one of the related factors for the M2 polarization of macrophages which can promote the progression and invasion and metastasis of tumors.

关 键 词：Ⅰ型胶原蛋白 巨噬细胞 结直肠癌 极化 实时定量聚合酶链反应 人 小鼠 

分 类 号：R735.3[医药卫生—肿瘤]