Cancer-associated hypersialylated MUC1 drives the differentiation of human monocytes into macrophages with a pathogenic phenotype

被引：49

作者：

Beatson, Richard ^{[1
]}

Graham, Rosalind ^{[1
]}

Grundland Freile, Fabio ^{[1
]}

Cozzetto, Domenico ^{[2
,3
]}

Kannambath, Shichina ^{[3
,4
]}

Pfeifer, Ester ^{[1
]}

Woodman, Natalie ^{[5
]}

Owen, Julie ^{[5
]}

Nuamah, Rosamond ^{[3
,4
]}

Mandel, Ulla ^{[6
,7
]}

Pinder, Sarah ^{[8
]}

Gillett, Cheryl ^{[5
]}

Noll, Thomas ^{[9
,10
]}

Bouybayoune, Ihssane ^{[8
]}

Taylor-Papadimitriou, Joyce ^{[1
]}

Burchell, Joy M. ^{[1
]}

机构：

[1] Kings Coll London, Guys Canc Ctr, Guys Hosp, Breast Canc Biol,Comprehens Canc Ctr, London SE1 9RT, England

[2] Guys & St Thomas NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr, Translat Bioinformat,Genom Facil, London SE1 9RT, England

[3] Kings Coll London, London SE1 9RT, England

[4] Guys & St Thomas NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr, Genom Facil, London SE1 9RT, England

[5] Kings Coll London, Guys Canc Ctr, Guys Hosp, KHP Tissue Bank,Breast Pathol,Comprehens Canc Ctr, London SE1 9RT, England

[6] Univ Copenhagen, Fac Hlth Sci, Dept Cellular & Mol Med, Copenhagen Ctr Glyc, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark

[7] Univ Copenhagen, Fac Hlth Sci, Dept Odontol, Copenhagen Ctr Glyc, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark

[8] Kings Coll London, Guys Canc Ctr, Guys Hosp, Breast Pathol,Comprehens Canc Ctr, London SE1 9RT, England

[9] Bielefeld Univ, Fac Technol, Cell Culture Technol, POB 10 01 31, D-33501 Bielefeld, Germany

[10] Bielefeld Univ, CeBiTec, POB 10 01 31, D-33501 Bielefeld, Germany

来源：

COMMUNICATIONS BIOLOGY | 2020年 / 3卷 / 01期

基金：

英国医学研究理事会;

关键词：

TUMOR-ASSOCIATED MACROPHAGES; BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; CARCINOMA-CELLS; O-GLYCAN; T-CELLS; PROGRESSION; NEUTROPHILS; EXPRESSION; GLYCOSYLATION;

D O I：

10.1038/s42003-020-01359-5

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

共 98 条

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