Extracellular matrix protein signaling promotes multi-step cancer vasculogenic mimicry formation

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dc.catalogadorjca
dc.contributor.authorMingo Orsini, Gabriel Antonio
dc.contributor.authorValdivia Román, Andrés Felipe
dc.contributor.authorSantander Zambrano, Gema Nicolle
dc.contributor.authorBabbitt Negrete, Nicole Anike
dc.contributor.authorAldana Villarroel, Varina Isabel
dc.contributor.authorPradenas Mateluna, Javiera Macarena Guillerm
dc.contributor.authorGonzález, Pamela
dc.contributor.authorCanales Valenzuela, Cristóbal
dc.contributor.authorToledo, Jorge A.
dc.contributor.authorIbáñez, Carolina
dc.contributor.authorNualart, Francisco
dc.contributor.authorVaras-Godoy, Manuel
dc.contributor.authorGejman, Roger
dc.contributor.authorRoa, Juan Carlos
dc.contributor.authorRavasio, Andrea
dc.contributor.authorBertocchi, Cristina
dc.contributor.authorOwen, Gareth Ivor
dc.date.accessioned2025-10-21T15:56:05Z
dc.date.available2025-10-21T15:56:05Z
dc.date.issued2025
dc.date.updated2025-10-12T00:04:11Z
dc.description.abstractCancer vasculogenic mimicry (VM) is the formation of vasculature structures in the absence of endothelial cells. We previously established an in vitro model that facilitates the formation of a lumen-containing and fluid-conducting tubular structures after 4 days of cancer cell growth on Matrigel. Herein, we mechanistically characterize this model in breast and ovarian cancer cell lines demonstrating distinct phases of VM formation and the dependence of specific extracellular matrix proteins. We report that VM occurs in four distinct stages. Firstly, alignment, migration then clustering delineate the area of the future tubular structure. Secondly, contraction of aligned structures followed by loss of attachment of some cells and cellular blebbing. Thirdly, a phase of mass proliferation followed by the raising of specific areas of the cancer cell mass above the Matrigel (bridge). Finally, the formation of a cell monolayer closes the tubular structure, forms a glycoprotein-rich luminal lining, then elevates the structure. Only later stages of VM require AKT and FAK signaling, as confirmed by chemical inhibition and phosphorylation analysis. We demonstrate that the lining of the tubular lumen is rich in laminin. Furthermore, the presence of Laminin 111 (but not collagen I) is sufficient in the extracellular matrix (Matrigel) for VM to occur and we confirm that integrin β1, but not integrin β3, is required and this protein changes location during the formation process. RNASeq analysis suggests that VM formation principally occurs through post-transcriptional regulation. As VM is associated with poor patient survival VM, an understanding of the mechanism of VM may bring to light novel biomarkers and anticancer targets.
dc.fechaingreso.objetodigital2025-10-12
dc.format.extent21 páginas
dc.fuente.origenBiomed Central
dc.identifier.issn1478-811X
dc.identifier.urihttps://doi.org/10.1186/s12964-025-02428-0
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/106288
dc.information.autorucFacultad de Ciencias Biológicas; Mingo Orsini, Gabriel Antonio; S/I; 221050
dc.information.autorucFacultad de Ciencias Biológicas; Valdivia Román, Andrés Felipe; S/I; 193501
dc.information.autorucFacultad de Ciencias Biológicas; Santander Zambrano, Gema Nicolle; S/I; 1246342
dc.information.autorucFacultad de Ciencias Biológicas; Babbitt Negrete, Nicole Anike; S/I; 1047221
dc.information.autorucInstituto de Ingeniería Biológica y Médica; Aldana Villarroel, Varina Isabel; S/I; 247433
dc.information.autorucFacultad de Ciencias Biológicas; Pradenas Mateluna, Javiera Macarena Guillerm; S/I; 1027773
dc.information.autorucFacultad de Ciencias Biológicas; Canales Valenzuela, Cristóbal; S/I; 1088997
dc.information.autorucFacultad de Ciencias Biológicas; Bertocchi, Cristina; 0000-0003-0907-1318; 1078032
dc.information.autorucFacultad de Ciencias Biológicas; Owen, Gareth Ivor; 0000-0003-3807-6054; 1000459
dc.issue.numero422
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaCell Communicationand Signaling
dc.rightsacceso abierto
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectVasculogenic mimicry
dc.subjectOvarian cancer
dc.subjectBreast cancer
dc.subjectExtracellular matrix
dc.subjectIntegrins
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleExtracellular matrix protein signaling promotes multi-step cancer vasculogenic mimicry formation
dc.typeartículo
dc.volumen23
sipa.codpersvinculados221050
sipa.codpersvinculados193501
sipa.codpersvinculados1246342
sipa.codpersvinculados1047221
sipa.codpersvinculados247433
sipa.codpersvinculados1027773
sipa.codpersvinculados1088997
sipa.codpersvinculados1078032
sipa.codpersvinculados1000459
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