Differential transplantability of human endothelial cells in colorectal cancer and renal cell carcinoma primary xenografts

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dc.contributor.authorSanz, Laura
dc.contributor.authorCuesta Martínez, Ángel
dc.contributor.authorSalas, Clara
dc.contributor.authorCorbacho, César
dc.contributor.authorBellas, Carmen
dc.contributor.authorÁlvarez-Vallina, Luís
dc.date.accessioned2024-01-18T16:03:02Z
dc.date.available2024-01-18T16:03:02Z
dc.date.issued2008-11-10
dc.description.abstractIn vivo models of human tumor vasculature are essential for the study of tumor angiogenesis and validation of therapeutic targets. To date, however, few standardized animal models of human tumor angiogenesis have been characterized. It was recently shown that human renal cell and prostate carcinoma primary xenografts, established from biopsy specimens, contained vessels lined mainly by human endothelial cells 1 month after implantation in immunodeficient mice. We selected colorectal cancer (CRC) as a primary xenograft model and studied the response of the vascular compartment to the new microenvironment during the same lapse of time. Immunohistochemical analysis of the origin of endothelial cells demonstrated that, in contrast to the mentioned study, human endothelial cells were rapidly substituted by their murine counterparts (nearly 50% by day 10 after implantation). Apoptotic human endothelial cells could not be detected 10 days after implantation, suggesting that apoptosis is not the mechanism underlying their replacement. Interestingly, host endothelial cells were found to colocalize with human laminin, suggesting a colonization of human vascular basement membranes after human endothelial cell disappearance. To rule out that the differences observed between the fate of human vasculature in the CRC model and those previously reported were because of methodological aspects, we established renal cell carcinoma (RCC) primary xenografts using the same protocol. In clear contrast with CRC xenografts, vasculature within RCC xenografts was mostly of human origin 35 days after implantation. These results support the notion of angiogenic heterogeneity in malignant neoplasms. Elucidation of the molecular mechanisms that determine persistence or disappearance of human endothelial cells in different tumor contexts can help to shed light on the intimate regulation of the angiogenic process.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipFondo de Investigación Sanitaria
dc.description.sponsorshipMinisterio de de Ciencia e Innovación (España)
dc.description.sponsorshipComunidad Autónoma de Madrid
dc.description.sponsorshipFundación Mutua Madrileña
dc.description.statuspub
dc.identifier.citationSanz L, Cuesta AM, Salas C, Corbacho C, Bellas C, Alvarez-Vallina L. Differential transplantability of human endothelial cells in colorectal cancer and renal cell carcinoma primary xenografts. Lab Invest. 2009;89(1):91-97. doi:10.1038/labinvest.2008.108
dc.identifier.doi10.1038/labinvest.2008.108
dc.identifier.essn1530-0307
dc.identifier.issn0023-6837
dc.identifier.officialurlhttps://doi.org/10.1038/labinvest.2008.108
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93914
dc.journal.titleLaboratory Investigation (LI)
dc.language.isoeng
dc.page.final97
dc.page.initial91
dc.publisherElsevier
dc.relation.projectIDinfo:eu-repo/grantAgreement/PI061621
dc.relation.projectIDinfo:eu-repo/grantAgreement/BIO2005-04794
dc.relation.projectIDinfo:eu-repo/grantAgreement/S-BIO-0236-2006
dc.rights.accessRightsrestricted access
dc.subject.keywordAnimal model
dc.subject.keywordendothelium
dc.subject.keywordprimary human xenograft
dc.subject.keywordtumor angiogenesis
dc.subject.keywordtumor microenvironment
dc.subject.keywordvascular remodeling
dc.subject.ucmCiencias Biomédicas
dc.subject.unesco24 Ciencias de la Vida
dc.titleDifferential transplantability of human endothelial cells in colorectal cancer and renal cell carcinoma primary xenografts
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number89
dspace.entity.typePublication
relation.isAuthorOfPublication963e050e-5a67-40d7-8e25-3dc7ff5a8619
relation.isAuthorOfPublication.latestForDiscovery963e050e-5a67-40d7-8e25-3dc7ff5a8619
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