title: The Wilms' tumour suppressor Wt1 is a major regulator of tumour angiogenesis and progression.
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.
authors.affiliation: Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, 06107 Nice, France.
authors.forename: Kay-Dietrich
authors.initials: KD
authors.lastname: Wagner
authors.affiliation: Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, 06107 Nice, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Cherfils-Vicini
authors.affiliation: Division of Health Sciences, Osaka University Graduate School of Medicine, 565-0871 Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosen
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenstein
authors.affiliation: 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.
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Hastie
authors.affiliation: 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.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Michiels
authors.affiliation: Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, 06107 Nice, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wagner
mesh_terms: D000818:Animals; D018450:Disease Progression; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D008546:Melanoma, Experimental / Q000098:blood supply / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D016019:Survival Analysis; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D034741:RNA, Small Interfering; D025721:WT1 Proteins; D019009:Proto-Oncogene Proteins c-kit