Endothelial Calcineurin Signaling Restrains Metastatic Outgrowth by Regulating Bmp2
| Autor: | Stefanie Hendrikx, Holger Gerhardt, Sina Nassiri, Borja Prat-Luri, Laureline Wetterwald, Claudio A. Franco, Nadine Zangger, Sanja Coso, Tatiana V. Petrova, Mauro Delorenzi, Amélie Sabine |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
vessels Lung Neoplasms Angiogenesis Cellular differentiation activated t-cells Bone Morphogenetic Protein 2 NUCLEAR-FACTOR ANGIOGENESIS Metastasis angiogenesis Mice 0302 clinical medicine NFAT Pathway VESSELS TRANSCRIPTION FACTOR Neoplasm Metastasis Melanoma lcsh:QH301-705.5 transcription factor vegf Neovascularization Pathologic Calcineurin Cell Differentiation NFAT VEGF 3. Good health medicine.anatomical_structure Neoplasm Micrometastasis nuclear-factor GROWTH Life Sciences & Biomedicine Signal Transduction EXPRESSION Endothelium growth ACTIVATED T-CELLS MATURATION General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Cell Line Tumor expression medicine Animals Humans Cell Proliferation Science & Technology STABILITY maturation business.industry Endothelial Cells Retinal Vessels Cell Biology stability medicine.disease 030104 developmental biology Animals Newborn lcsh:Biology (General) Cardiovascular and Metabolic Diseases Bone Morphogenetic Protein 2/metabolism Calcineurin/metabolism Endothelial Cells/metabolism Lung Neoplasms/secondary Melanoma/pathology Neovascularization Pathologic/metabolism Retinal Vessels/metabolism BMP2 calcineurin endothelial melanoma metastasis Cancer cell Cancer research business 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 26, Iss 5, Pp 1227-1241.e6 (2019) Cell reports, vol. 26, no. 5, pp. 1227-1241.e6 Cell Reports |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2019.01.016 |
| Popis: | Summary: 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. : Hendrikx et al. show that endothelial calcineurin signaling is dispensable for physiological and tumor angiogenesis. Instead, it promotes vascular stabilization and, in cancer, restrains metastatic outgrowth. Immunosuppressive therapy with calcineurin inhibitors thus also directly affects the endothelium, which may contribute to aggressive cancer progression in organ transplant recipients. Keywords: angiogenesis, calcineurin, NFAT, BMP2, endothelial, metastasis, melanoma |
| Databáze: | OpenAIRE |
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