Cancer-associated hypersialylated MUC1 drives the differentiation of human monocytes into macrophages with a pathogenic phenotype.
Cancer-associated hypersialylated MUC1 drives the differentiation of human monocytes into macrophages with a pathogenic phenotype.
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与癌症相关的高含量的MUC1驱动人类单核细胞分化为具有致病表型的巨噬细胞。
DOI：
10.1038/s42003-020-01359-5
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发表时间：
2020-11-04
影响因子：
5.9
通讯作者：
Burchell JM
中科院分区：
文献类型：
--
作者：
Beatson R;Graham R;Grundland Freile F;Cozzetto D;Kannambath S;Pfeifer E;Woodman N;Owen J;Nuamah R;Mandel U;Pinder S;Gillett C;Noll T;Bouybayoune I;Taylor-Papadimitriou J;Burchell JM
肿瘤微环境在肿瘤的生长和发展中起着至关重要的作用，肿瘤相关巨噬细胞(TAMs)的存在与预后不良有关。最近的研究表明，TAMS具有转录、表型、功能和地理多样性。在这里，我们展示了粘蛋白MUC1的唾液酸化的肿瘤相关糖形式，MUC1-ST，通过Siglec-9的参与，可以特异性和独立地诱导单核细胞分化为具有独特表型的TAM，据我们所知，这是以前没有描述过的。这些TAMs可以招募和延长中性粒细胞的寿命，抑制T细胞的功能，降解允许侵袭的基底膜，吞噬功能低下，并能诱导血浆凝血。这种巨噬细胞表型在乳腺癌巢边缘的间质中丰富，它们的存在与乳腺癌患者的预后不良有关。Beatson等人。结果表明，粘蛋白MUC1的一种与肿瘤相关的糖形蛋白诱导单核细胞分化为肿瘤相关的巨噬细胞。这些巨噬细胞在乳腺癌间质中被发现，它们的存在与预后不良有关。
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 have demonstrated that TAMs display 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 that to the best of our knowledge has not previously been described. These TAMs can recruit and prolong the lifespan of neutrophils, inhibit the function of T cells, degrade basement membrane allowing for invasion, are inefficient at phagocytosis, and can induce plasma clotting. This 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. Beatson et al. show that a sialylated tumour-associated glycoform of the mucin MUC1 induces the differentiation of monocytes into tumour-associated macrophages. These macrophages are found in breast cancer stroma and their presence is associated with poor prognosis.
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TLR与模式识别受体家族之间的广泛而直接的相互作用及其对NEU1的调节。
影响因子：
7.7
作者：
Chen GY;Brown NK;Wu W;Khedri Z;Yu H;Chen X;van de Vlekkert D;D'Azzo A;Zheng P;Liu Y
通讯作者：
Liu Y
影响因子：
64.8
作者：
Finisguerra V;Di Conza G;Di Matteo M;Serneels J;Costa S;Thompson AA;Wauters E;Walmsley S;Prenen H;Granot Z;Casazza A;Mazzone M
通讯作者：
Mazzone M
影响因子：
4.1
作者：
Bäckström, M;Link, T;Hansson, GC
通讯作者：
Hansson, GC
粘蛋白MUC1通过参与凝集素SIGLEC-9调节肿瘤免疫学微环境。
影响因子：
30.5
作者：
Beatson R;Tajadura-Ortega V;Achkova D;Picco G;Tsourouktsoglou TD;Klausing S;Hillier M;Maher J;Noll T;Crocker PR;Taylor-Papadimitriou J;Burchell JM
通讯作者：
Burchell JM
DOI：
10.1126/science.1168988
发表时间：
2009-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen GY;Tang J;Zheng P;Liu Y
通讯作者：
Liu Y