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Inactivation of EMILIN-1 by Proteolysis and Secretion in Small Extracellular Vesicles Favors Melanoma Progression and Metastasis

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Názov: Inactivation of EMILIN-1 by Proteolysis and Secretion in Small Extracellular Vesicles Favors Melanoma Progression and Metastasis
Autori: Amor López, Ana, Mazariegos, Marina S., Capuano, Alessandra, Hergueta-Redondo, Marta, Recio Conde, Juan Angel, Muñoz Couselo, Eva, Ximénez-Embún, Pilar
Prispievatelia: Institut Català de la Salut, Amor López A, Mazariegos MS, Hergueta-Redondo M Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain. Capuano A Unit of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), Department of Advanced Cancer Research and Diagnostics, IRCCS, I-33081 Aviano, Italy. Ximénez-Embún P Proteomics Unit—ProteoRed-ISCIII, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain. Recio JÁ Laboratori de Recerca Biomèdica en Melanoma-Models Animals i Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Muñoz J Clinical Oncology Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus
Zdroj: Scientia
Informácie o vydavateľovi: MDPI
Rok vydania: 2021
Predmety: Metàstasi limfàtica, Cèl·lules canceroses - Proliferació, Ratolins, DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis::Lymphatic Metastasis, PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cell Growth Processes::Cell Proliferation, ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice, ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica::metástasis linfática, FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::procesos de crecimiento celular::proliferación celular, ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones
Popis: EMILIN-1; Melanoma; Metàstasi ; EMILIN-1; Melanoma; Metástasis ; EMILIN-1; Melanoma; Metastasis ; Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not completely defined. Here, we found that EMILIN-1 is proteolyzed and secreted in small EVs (sEVs) as a novel mechanism to reduce its intracellular levels favoring metastasis in mouse melanoma lymph node metastatic cells. Interestingly, we observed that EMILIN-1 has intrinsic tumor and metastasis suppressive-like properties reducing effective migration, cell viability, primary tumor growth, and metastasis. Overall, our analysis suggests that the inactivation of EMILIN-1 by proteolysis and secretion in sEVs reduce its intrinsic tumor suppressive activities in melanoma favoring tumor progression and metastasis. ; The authors gratefully acknowledge the support of the following sources of funding: Fundación Ramon Areces, MINECO (SAF2014-54541-R), Ramón y Cajal Programme, Asociación Española Contra el Cáncer, Constantes y Vitales (ATRES MEDIA/AXA Foundation) and FERO Foundation. We are also grateful for the support of the support of the Translational NeTwork for the CLinical application of Extracellular VesicleS, TeNTaCLES. RED2018-102411-T (AEI/10.13039/501100011033) and MINECO-Severo Ochoa predoctoral program to support A.A.L thesis and short term stay in Italy to perform this study. The CNIO, certified as Severo Ochoa Excellence Centre, is supported by the Spanish Government through the Instituto de Salud Carlos III (ISCIII).
Druh dokumentu: article in journal/newspaper
Popis súboru: application/pdf; image/tiff
Jazyk: English
ISSN: 34299025
Relation: International Journal of Molecular Sciences;22(14); https://doi.org/10.3390/ijms22147406; https://hdl.handle.net/11351/6946; 000676246500001
DOI: 10.3390/ijms22147406
Dostupnosť: https://hdl.handle.net/11351/6946
https://doi.org/10.3390/ijms22147406
Rights: Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/openAccess
Prístupové číslo: edsbas.C8B9BF0E
Databáza: BASE
Popis
Abstrakt:EMILIN-1; Melanoma; Metàstasi ; EMILIN-1; Melanoma; Metástasis ; EMILIN-1; Melanoma; Metastasis ; Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not completely defined. Here, we found that EMILIN-1 is proteolyzed and secreted in small EVs (sEVs) as a novel mechanism to reduce its intracellular levels favoring metastasis in mouse melanoma lymph node metastatic cells. Interestingly, we observed that EMILIN-1 has intrinsic tumor and metastasis suppressive-like properties reducing effective migration, cell viability, primary tumor growth, and metastasis. Overall, our analysis suggests that the inactivation of EMILIN-1 by proteolysis and secretion in sEVs reduce its intrinsic tumor suppressive activities in melanoma favoring tumor progression and metastasis. ; The authors gratefully acknowledge the support of the following sources of funding: Fundación Ramon Areces, MINECO (SAF2014-54541-R), Ramón y Cajal Programme, Asociación Española Contra el Cáncer, Constantes y Vitales (ATRES MEDIA/AXA Foundation) and FERO Foundation. We are also grateful for the support of the support of the Translational NeTwork for the CLinical application of Extracellular VesicleS, TeNTaCLES. RED2018-102411-T (AEI/10.13039/501100011033) and MINECO-Severo Ochoa predoctoral program to support A.A.L thesis and short term stay in Italy to perform this study. The CNIO, certified as Severo Ochoa Excellence Centre, is supported by the Spanish Government through the Instituto de Salud Carlos III (ISCIII).
ISSN:34299025
DOI:10.3390/ijms22147406