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The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages.
- Source :
-
Nature communications [Nat Commun] 2016 May 06; Vol. 7, pp. 11385. Date of Electronic Publication: 2016 May 06. - Publication Year :
- 2016
-
Abstract
- Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy.
- Subjects :
- Animals
Becaplermin
Cell Line, Tumor
Female
Humans
Interleukin-33 genetics
Mice
Mice, Inbred C57BL
Neoplasm Metastasis
Neoplasms genetics
Neoplasms metabolism
Neoplasms pathology
SOXF Transcription Factors genetics
Interleukin-33 metabolism
Macrophages metabolism
Pericytes metabolism
Proto-Oncogene Proteins c-sis metabolism
SOXF Transcription Factors metabolism
Stromal Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 27150562
- Full Text :
- https://doi.org/10.1038/ncomms11385