Endothelial Calcineurin Signaling Restrains Metastatic Outgrowth by Regulating Bmp2.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_B316C6C93CB8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Endothelial Calcineurin Signaling Restrains Metastatic Outgrowth by Regulating Bmp2.
Journal
Cell reports
Author(s)
Hendrikx S., Coso S., Prat-Luri B., Wetterwald L., Sabine A., Franco C.A., Nassiri S., Zangger N., Gerhardt H., Delorenzi M., Petrova T.V.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
29/01/2019
Peer-reviewed
Oui
Volume
26
Number
5
Pages
1227-1241.e6
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Calcineurin/NFAT signaling is active in endothelial cells and is proposed to be an essential component of the tumor angiogenic response. Here, we investigated the role of endothelial calcineurin signaling in vivo in physiological and pathological angiogenesis and tumor metastasis. We show that this pathway is dispensable for retinal and tumor angiogenesis, but it is implicated in vessel stabilization. While ablation of endothelial calcineurin does not affect the progression of primary tumors or tumor cell extravasation, it does potentiate the outgrowth of lung metastases. We identify Bmp2 as a downstream target of the calcineurin/NFAT pathway in lung endothelium, potently inhibiting cancer cell growth by stimulating differentiation. We reveal a dual role of calcineurin/NFAT signaling in vascular regression or stabilization and in the tissue-specific production of an angiocrine factor restraining cancer cell outgrowth. Our results suggest that, besides targeting the immune system, post-transplantation immunosuppressive therapy with calcineurin inhibitors directly targets the endothelium, contributing to aggressive cancer progression.
Keywords
Animals, Animals, Newborn, Bone Morphogenetic Protein 2/metabolism, Calcineurin/metabolism, Cell Differentiation, Cell Line, Tumor, Cell Proliferation, Endothelial Cells/metabolism, Humans, Lung Neoplasms/secondary, Melanoma/pathology, Mice, Neoplasm Metastasis, Neoplasm Micrometastasis, Neovascularization, Pathologic/metabolism, Retinal Vessels/metabolism, Signal Transduction, BMP2, NFAT, angiogenesis, calcineurin, endothelial, melanoma, metastasis
Pubmed
Web of science
Open Access
Yes
Create date
27/02/2019 11:03
Last modification date
05/04/2020 5:20
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