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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
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.
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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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