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Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding
Endothelial cells (ECs) grant access of disseminated cancer cells to distant organs. However, the molecular players regulating the activation of quiescent ECs at the premetastatic niche (PMN) remain elusive. Here, we find that ECs at the PMN coexpress tumor necrosis factor–related apoptosis-inducing...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10032608/ https://www.ncbi.nlm.nih.gov/pubmed/36947620 http://dx.doi.org/10.1126/sciadv.add5028 |
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author | Riera-Domingo, Carla Leite-Gomes, Eduarda Charatsidou, Iris Zhao, Peihua Carrá, Giovanna Cappellesso, Federica Mourao, Larissa De Schepper, Maxim Liu, Dana Serneels, Jens Alameh, Mohamad-Gabriel Shuvaev, Vladimir V. Geukens, Tatjana Isnaldi, Edoardo Prenen, Hans Weissman, Drew Muzykantov, Vladimir R. Soenen, Stefaan Desmedt, Christine Scheele, Colinda L. G. J. Sablina, Anna Di Matteo, Mario Martín-Pérez, Rosa Mazzone, Massimiliano |
author_facet | Riera-Domingo, Carla Leite-Gomes, Eduarda Charatsidou, Iris Zhao, Peihua Carrá, Giovanna Cappellesso, Federica Mourao, Larissa De Schepper, Maxim Liu, Dana Serneels, Jens Alameh, Mohamad-Gabriel Shuvaev, Vladimir V. Geukens, Tatjana Isnaldi, Edoardo Prenen, Hans Weissman, Drew Muzykantov, Vladimir R. Soenen, Stefaan Desmedt, Christine Scheele, Colinda L. G. J. Sablina, Anna Di Matteo, Mario Martín-Pérez, Rosa Mazzone, Massimiliano |
author_sort | Riera-Domingo, Carla |
collection | PubMed |
description | Endothelial cells (ECs) grant access of disseminated cancer cells to distant organs. However, the molecular players regulating the activation of quiescent ECs at the premetastatic niche (PMN) remain elusive. Here, we find that ECs at the PMN coexpress tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and its cognate death receptor 5 (DR5). Unexpectedly, endothelial TRAIL interacts intracellularly with DR5 to prevent its signaling and preserve a quiescent vascular phenotype. In absence of endothelial TRAIL, DR5 activation induces EC death and nuclear factor κB/p38–dependent EC stickiness, compromising vascular integrity and promoting myeloid cell infiltration, breast cancer cell adhesion, and metastasis. Consistently, both down-regulation of endothelial TRAIL at the PMN by proangiogenic tumor-secreted factors and the presence of the endogenous TRAIL inhibitors decoy receptor 1 (DcR1) and DcR2 favor metastasis. This study discloses an intracrine mechanism whereby TRAIL blocks DR5 signaling in quiescent endothelia, acting as gatekeeper of the vascular barrier that is corrupted by the tumor during cancer cell dissemination. |
format | Online Article Text |
id | pubmed-10032608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-100326082023-03-23 Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding Riera-Domingo, Carla Leite-Gomes, Eduarda Charatsidou, Iris Zhao, Peihua Carrá, Giovanna Cappellesso, Federica Mourao, Larissa De Schepper, Maxim Liu, Dana Serneels, Jens Alameh, Mohamad-Gabriel Shuvaev, Vladimir V. Geukens, Tatjana Isnaldi, Edoardo Prenen, Hans Weissman, Drew Muzykantov, Vladimir R. Soenen, Stefaan Desmedt, Christine Scheele, Colinda L. G. J. Sablina, Anna Di Matteo, Mario Martín-Pérez, Rosa Mazzone, Massimiliano Sci Adv Biomedicine and Life Sciences Endothelial cells (ECs) grant access of disseminated cancer cells to distant organs. However, the molecular players regulating the activation of quiescent ECs at the premetastatic niche (PMN) remain elusive. Here, we find that ECs at the PMN coexpress tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and its cognate death receptor 5 (DR5). Unexpectedly, endothelial TRAIL interacts intracellularly with DR5 to prevent its signaling and preserve a quiescent vascular phenotype. In absence of endothelial TRAIL, DR5 activation induces EC death and nuclear factor κB/p38–dependent EC stickiness, compromising vascular integrity and promoting myeloid cell infiltration, breast cancer cell adhesion, and metastasis. Consistently, both down-regulation of endothelial TRAIL at the PMN by proangiogenic tumor-secreted factors and the presence of the endogenous TRAIL inhibitors decoy receptor 1 (DcR1) and DcR2 favor metastasis. This study discloses an intracrine mechanism whereby TRAIL blocks DR5 signaling in quiescent endothelia, acting as gatekeeper of the vascular barrier that is corrupted by the tumor during cancer cell dissemination. American Association for the Advancement of Science 2023-03-22 /pmc/articles/PMC10032608/ /pubmed/36947620 http://dx.doi.org/10.1126/sciadv.add5028 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Riera-Domingo, Carla Leite-Gomes, Eduarda Charatsidou, Iris Zhao, Peihua Carrá, Giovanna Cappellesso, Federica Mourao, Larissa De Schepper, Maxim Liu, Dana Serneels, Jens Alameh, Mohamad-Gabriel Shuvaev, Vladimir V. Geukens, Tatjana Isnaldi, Edoardo Prenen, Hans Weissman, Drew Muzykantov, Vladimir R. Soenen, Stefaan Desmedt, Christine Scheele, Colinda L. G. J. Sablina, Anna Di Matteo, Mario Martín-Pérez, Rosa Mazzone, Massimiliano Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding |
title | Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding |
title_full | Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding |
title_fullStr | Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding |
title_full_unstemmed | Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding |
title_short | Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding |
title_sort | breast tumors interfere with endothelial trail at the premetastatic niche to promote cancer cell seeding |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10032608/ https://www.ncbi.nlm.nih.gov/pubmed/36947620 http://dx.doi.org/10.1126/sciadv.add5028 |
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