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Cancer-associated hypersialylated MUC1 drives the differentiation of monocytes into macrophages with a pathogenic phenotype
- Publication Year :
- 2020
- Publisher :
- Cold Spring Harbor Laboratory, 2020.
-
Abstract
- 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.
- Subjects :
- 0303 health sciences
Phagocytosis
Mucin
Cancer
Biology
medicine.disease
Phenotype
3. Good health
Transcriptome
03 medical and health sciences
0302 clinical medicine
Stroma
030220 oncology & carcinogenesis
Cancer research
medicine
Macrophage
skin and connective tissue diseases
MUC1
030304 developmental biology
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....54750301380771f3f481101814e8bc14