Lactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities

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dc.catalogadorgjm
dc.contributor.authorDurán-Jara, Eduardo
dc.contributor.authorCampo, Matías del
dc.contributor.authorGutiérrez, Valentina
dc.contributor.authorWichmann Pérez, Ignacio Alberto
dc.contributor.authorTrigo, César
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorLobos-González, Lorena
dc.date.accessioned2024-01-08T18:57:03Z
dc.date.available2024-01-08T18:57:03Z
dc.date.issued2024
dc.date.updated2024-01-07T01:04:32Z
dc.description.abstractBackground: Tumor-derived small extracellular vesicles (sEVs) can promote tumorigenic and metastatic capacities in less aggressive recipient cells mainly through the biomolecules in their cargo. However, despite recent advances, the specific molecules orchestrating these changes are not completely defined. Lactadherin is a secreted glycoprotein typically found in the milk fat globule membrane. Its overexpression has been associated with increased tumorigenesis and metastasis in breast cancer (BC) and other tumors. However, neither its presence in sEVs secreted by BC cells, nor its role in sEV-mediated intercellular communication have been described. The present study focused on the role of lactadherin-containing sEVs from metastatic MDA-MB-231 triple-negative BC (TNBC) cells (sEV-MDA231) in the promotion of pro-metastatic capacities in non-tumorigenic and non-metastatic recipient cells in vitro, as well as their pro-metastatic role in a murine model of peritoneal carcinomatosis. Results: We show that lactadherin is present in sEVs secreted by BC cells and it is higher in sEV-MDA231 compared with the other BC cell-secreted sEVs measured through ELISA. Incubation of non-metastatic recipient cells with sEV-MDA231 increases their migration and, to some extent, their tumoroid formation capacity but not their anchorage-independent growth. Remarkably, lactadherin blockade in sEV-MDA231 results in a significant decrease of those sEV-mediated changes in vitro. Similarly, intraperitoneally treatment of mice with MDA-MB-231 BC cells and sEV-MDA231 greatly increase the formation of malignant ascites and tumor micronodules, effects that were significantly inhibited when lactadherin was previously blocked in those sEV-MDA231. Conclusions: As to our knowledge, our study provides the first evidence on the role of lactadherin in metastatic BC cell-secreted sEVs as promoter of: (i) metastatic capacities in less aggressive recipient cells, and ii) the formation of malignant ascites and metastatic tumor nodules. These results increase our understanding on the role of lactadherin in sEVs as promoter of metastatic capacities which can be used as a therapeutic option for BC and other malignancies.
dc.fechaingreso.objetodigital2024-01-08
dc.format.extent19 páginas
dc.fuente.origenBiomed Central
dc.identifier.citationBiological Research. 2024 Jan 03;57(1):1
dc.identifier.urihttps://doi.org/10.1186/s40659-023-00477-8
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/75652
dc.information.autorucEscuela de medicina; Wichmann Pérez, Ignacio Alberto; 0000-0002-1115-2937; 149908
dc.issue.numero1
dc.language.isoen
dc.language.rfc3066en
dc.nota.accesoContenido completo
dc.revistaBiological Research
dc.rightsacceso abierto
dc.rights.holderThe Author(s)
dc.rights.licenseCC BY 4.0 DEED Attribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBreast cancer
dc.subjectExtracellular vesicles
dc.subjectLactadherin
dc.subjectMetastasis
dc.titleLactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities
dc.typeartículo
dc.volumen57
sipa.codpersvinculados149908
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