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Nat Commun. 2014 Dec 16;5:5852. doi: 10.1038/ncomms6852.

The Wilms' tumour suppressor Wt1 is a major regulator of tumour angiogenesis and progression.

Author information

1
Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, 06107 Nice, France.
2
Division of Health Sciences, Osaka University Graduate School of Medicine, 565-0871 Osaka, Japan.
3
The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK.
4
1] Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, 06107 Nice, France [2] Department of Medical Genetics, CHU Nice, Nice 06202, France.
5
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
6
1] Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, 06107 Nice, France [2] Department of Pathology, CHU Nice, 06002 Nice, France.

Abstract

Angiogenesis, activation of metastasis and avoidance of immune destruction are important for cancer progression. These biological capabilities are, apart from cancer cells, mediated by different cell types, including endothelial, haematopoietic progenitor and myeloid-derived suppressor cells. We show here that all these cell types frequently express the Wilms' tumour suppressor Wt1, which transcriptionally controls expression of Pecam-1 (CD31) and c-kit (CD117). Inducible conditional knockout of Wt1 in endothelial, haematopoietic and myeloid-derived suppressor cells is sufficient to cause regression of tumour vascularization and an enhanced immune response, leading to decreased metastasis, regression of established tumours and enhanced survival. Thus, Wt1 is an important regulator of cancer growth via modulation of tumour vascularization, immune response and metastasis formation.

PMID:
25510679
DOI:
10.1038/ncomms6852
[Indexed for MEDLINE]

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