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Wilms 瘤抑制因子 WT1 是肿瘤血管生成和进展的主要调节因子。

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

机构信息

Institute for Research on Cancer and Aging, Nice (IRCAN), Faculty of Medicine, University of Nice Sophia-Antipolis, CNRS UMR7284/INSERM U1081, 06107 Nice, France.

Division of Health Sciences, Osaka University Graduate School of Medicine, 565-0871 Osaka, Japan.

出版信息

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

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.

摘要

血管生成、转移的激活和避免免疫破坏对于癌症的进展很重要。除了癌细胞外,这些生物学功能还由不同的细胞类型介导,包括内皮细胞、造血祖细胞和髓系来源的抑制细胞。我们在这里表明,所有这些细胞类型经常表达 Wilms 肿瘤抑制因子 Wt1,该因子转录控制 Pecam-1(CD31)和 c-kit(CD117)的表达。内皮细胞、造血细胞和髓系来源的抑制细胞中 Wt1 的诱导性条件性敲除足以引起肿瘤血管生成的消退和免疫反应的增强,从而导致转移减少、已建立的肿瘤消退和生存时间的延长。因此,Wt1 通过调节肿瘤血管生成、免疫反应和转移形成,是癌症生长的重要调节剂。

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