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| Item Type: | Article |
|---|---|
| Title: | Endothelial calcineurin signaling restrains metastatic outgrowth by regulating Bmp2 |
| Creators Name: | Hendrikx, S. and Coso, S. and Prat-Luri, B. and Wetterwald, L. and Sabine, A. and Franco, C.A. and Nassiri, S. and Zangger, N. and Gerhardt, H. and Delorenzi, M. and Petrova, T.V. |
| 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: | Angiogenesis, Calcineurin, NFAT, BMP2, Endothelial, Metastasis, Melanoma, Animals, Mice |
| Source: | Cell Reports |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 26 |
| Number: | 5 |
| Page Range: | 1227-1241 |
| Date: | 29 January 2019 |
| Official Publication: | https://doi.org/10.1016/j.celrep.2019.01.016 |
| PubMed: | View item in PubMed |
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