| Literature DB >> 28238683 |
Elfriede Wieland1, Juan Rodriguez-Vita1, Sven S Liebler2, Carolin Mogler3, Iris Moll1, Stefanie E Herberich2, Elisa Espinet4, Esther Herpel5, Amitai Menuchin6, Jenny Chang-Claude7, Michael Hoffmeister8, Christoffer Gebhardt9, Hermann Brenner10, Andreas Trumpp4, Christian W Siebel11, Markus Hecker12, Jochen Utikal9, David Sprinzak6, Andreas Fischer13.
Abstract
Endothelial cells (ECs) provide angiocrine factors orchestrating tumor progression. Here, we show that activated Notch1 receptors (N1ICD) are frequently observed in ECs of human carcinomas and melanoma, and in ECs of the pre-metastatic niche in mice. EC N1ICD expression in melanoma correlated with shorter progression-free survival. Sustained N1ICD activity induced EC senescence, expression of chemokines and the adhesion molecule VCAM1. This promoted neutrophil infiltration, tumor cell (TC) adhesion to the endothelium, intravasation, lung colonization, and postsurgical metastasis. Thus, sustained vascular Notch signaling facilitates metastasis by generating a senescent, pro-inflammatory endothelium. Consequently, treatment with Notch1 or VCAM1-blocking antibodies prevented Notch-driven metastasis, and genetic ablation of EC Notch signaling inhibited peritoneal neutrophil infiltration in an ovarian carcinoma mouse model.Entities:
Keywords: Notch signaling; angiogenesis; endothelial cell; extravasation; intravasation; metastasis; mouse models; neutrophils; senescence; vascular biology
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Year: 2017 PMID： 28238683 DOI： 10.1016/j.ccell.2017.01.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743