Cancer-associated hypersialylated MUC1 drives the differentiation of monocytes into macrophages with a pathogenic phenotype
Cancer-associated hypersialylated MUC1 drives the differentiation of monocytes into macrophages with a pathogenic phenotype
复制标题
癌症相关的高唾液酸化 MUC1 驱动单核细胞分化为具有致病表型的巨噬细胞
DOI：
10.1101/2020.05.06.080713
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Beatson R
中科院分区：
文献类型：
--
作者：
Beatson R
肿瘤微环境在癌症的生长和进展中起着至关重要的作用，肿瘤相关巨噬细胞（TAM）的存在与预后不良有关。最近的研究表明，TAM显示转录组，表型，功能和地理多样性。在这里，我们表明粘蛋白MUC 1的唾液酸化肿瘤相关糖型MUC 1-ST通过Siglec-9的参与可以特异性地和独立地诱导单核细胞分化为具有独特表型的TAM。这些TAM可以募集和维持嗜中性粒细胞，抑制T细胞的功能，降解基底膜以允许侵入，在吞噬作用方面效率低下，并且可以诱导血浆凝血。这种新的巨噬细胞表型在乳腺癌巢边缘的基质中富集，并且它们的存在与乳腺癌患者的不良预后相关。
The tumour microenvironment plays a crucial role in the growth and progression of cancer and the presence of tumour-associated macrophages (TAMs) is associated with poor prognosis. Recent studies show that TAMs show transcriptomic, phenotypic, functional and geographical diversity. Here we show that a sialylated tumour-associated glycoform of the mucin MUC1, MUC1-ST, through the engagement of Siglec-9 can specifically and independently induce the differentiation of monocytes into TAMs with a unique phenotype. These TAMs can recruit and maintain neutrophils, inhibit the function of T cells, degrade basement membrane allowing for invasion, are inefficient at phagocytosis, and can induce plasma clotting. This novel macrophage phenotype is enriched in the stroma at the edge of breast cancer nests and their presence is associated with poor prognosis in breast cancer patients.