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 |
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| Autori: | Ana Amor López, Marina S. Mazariegos, Alessandra Capuano, Pilar Ximénez-Embún, Marta Hergueta-Redondo, Juan Ángel Recio, Eva Muñoz, Fátima Al-Shahrour, Javier Muñoz, Diego Megías, Roberto Doliana, Paola Spessotto, Héctor Peinado |
| 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: | Int J Mol Sci Scientia Scientia. Dipòsit d'Informació Digital del Departament de Salut instname International Journal of Molecular Sciences; Volume 22; Issue 14; Pages: 7406 |
| Informácie o vydavateľovi: | Cold Spring Harbor Laboratory, 2021. |
| Rok vydania: | 2021 |
| Predmety: | Male, 0301 basic medicine, Cell Survival, Cèl·lules canceroses - Proliferació, Metàstasi limfàtica, Real-Time Polymerase Chain Reaction, ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones, Article, Mass Spectrometry, Statistics, Nonparametric, DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis::Lymphatic Metastasis, Extracellular Vesicles, Mice, 03 medical and health sciences, Cell Movement, Cell Line, Tumor, Animals, Ratolins, RNA-Seq, EMILIN-1, small extracellular vesicles, metastasis, melanoma, Melanoma, Cell Proliferation, 0303 health sciences, Membrane Glycoproteins, ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica::metástasis linfática, FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::procesos de crecimiento celular::proliferación celular, Computational Biology, Xenograft Model Antitumor Assays, Up-Regulation, 3. Good health, Mice, Inbred C57BL, Lymphatic Metastasis, Proteolysis, PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cell Growth Processes::Cell Proliferation, ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice |
| Popis: | Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not defined completely. 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 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 in mouse melanoma models. Finally, analysis in human melanoma samples showed that tumor cells with high levels of EMILIN-1 are reduced in metastatic lesions compared to primary tumors or nevi. 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. |
| Druh dokumentu: | Article Other literature type |
| Popis súboru: | application/pdf; image/tiff |
| ISSN: | 1422-0067 |
| DOI: | 10.1101/2021.06.02.446715 |
| DOI: | 10.3390/ijms22147406 |
| Prístupová URL adresa: | https://www.biorxiv.org/content/biorxiv/early/2021/06/02/2021.06.02.446715.full.pdf https://www.mdpi.com/1422-0067/22/14/7406/pdf https://pubmed.ncbi.nlm.nih.gov/34299025 https://hdl.handle.net/11351/6946 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303474 https://www.mdpi.com/1422-0067/22/14/7406/pdf https://www.mdpi.com/1422-0067/22/14/7406 https://europepmc.org/article/PPR/PPR351878 https://www.biorxiv.org/content/10.1101/2021.06.02.446715v1 https://biorxiv.org/content/10.1101/2021.06.02.446715v1.full.pdf |
| Rights: | CC BY NC ND CC BY |
| Prístupové číslo: | edsair.doi.dedup.....b5843db32d4ebbd2a661a44ae946d64d |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not defined completely. 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 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 in mouse melanoma models. Finally, analysis in human melanoma samples showed that tumor cells with high levels of EMILIN-1 are reduced in metastatic lesions compared to primary tumors or nevi. 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. |
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| ISSN: | 14220067 |
| DOI: | 10.1101/2021.06.02.446715 |