New Insights into the Exosome-Induced Migration of Uveal Melanoma Cells and the Pre-Metastatic Niche Formation in the Liver

UM is an aggressive intraocular tumor characterized by high plasticity and a propensity to metastasize in the liver. However, the underlying mechanisms governing liver tropism remain poorly understood. Given the emerging significance of exosomes, we sought to investigate the contribution of UM-deriv...

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Detalles Bibliográficos
Autores: Ramos, Raquel, Vinyals, Antònia|||0000-0003-3925-0050, Campos-Martin, Rafael|||0000-0002-1395-8571, Cabré i Gelada, Eduard|||0000-0002-1807-6981, Bech-Serra, Joan-Josep|||0000-0003-3486-781X, Vaquero, Javier, Gonzalez-Sanchez, Ester|||0000-0002-9636-9624, Bertran Rodríguez, Esther|||0000-0001-9356-7409, Ferreres, Josep Ramon, Lorenzo, Daniel|||0000-0001-7545-7257, De La Torre, Carolina G., Fabregat, Isabel|||0000-0003-0136-8440, Caminal, J.M.|||0000-0001-9563-0344, Fabra Fres, Àngels
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:311567
Acceso en línea:https://ddd.uab.cat/record/311567
https://dx.doi.org/urn:doi:10.3390/cancers16172977
Access Level:acceso abierto
Palabra clave:Uveal melanoma
Exosomes
Hepatic stellate cells
Macrophages
Liver metastasis
Mesenchymal migration
Amoeboid migration
Descripción
Sumario:UM is an aggressive intraocular tumor characterized by high plasticity and a propensity to metastasize in the liver. However, the underlying mechanisms governing liver tropism remain poorly understood. Given the emerging significance of exosomes, we sought to investigate the contribution of UM-derived exosomes to specific steps of the metastatic process. Firstly, we isolated exosomes from UM cells sharing a common genetic background and different metastatic properties. A comparison of protein cargo reveals an overrepresentation of proteins related to cytoskeleton remodeling and actin filament-based movement in exosomes derived from the parental cells that may favor the detachment of cells from the primary site. Secondly, we assessed the role of macrophages in reprogramming the HHSCs by exosomes. The activation of HHSCs triggered a pro-inflammatory and pro-fibrotic environment through cytokine production, upregulation of extracellular matrix molecules, and the activation of signaling pathways. Finally, we found that activated HHSCs promote increased adhesion and migration of UM cells. Our findings shed light on the pivotal role of exosomes in pre-metastatic niche construction in the liver.

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