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dc.contributor.authorAlonso-Alconada, Lorena
dc.contributor.authorMuinelo-Romay, Laura
dc.contributor.authorMadissoo, Kadri
dc.contributor.authorDíaz-López, Antonio
dc.contributor.authorKrakstad, Camilla
dc.contributor.authorTrovik, Jone
dc.contributor.authorWik, Elisabeth
dc.contributor.authorHapangama, Dharani
dc.contributor.authorCoenegrachts, Lieve
dc.contributor.authorCano, Amparo
dc.contributor.authorGil-Moreno, Antonio
dc.contributor.authorChiva, Luís
dc.contributor.authorCueva, Juan
dc.contributor.authorVieito, María
dc.contributor.authorOrtega Izquierdo, Maria Eugenia
dc.contributor.authorMariscal, Javier
dc.contributor.authorColas, Eva
dc.contributor.authorCastellví, Josep
dc.contributor.authorCusido, Maite
dc.contributor.authorDolcet Roca, Xavier
dc.contributor.authorNijman, Hans W.
dc.contributor.authorBosse, Tjalling
dc.contributor.authorGreen, John A.
dc.contributor.authorRomano, Andrea
dc.contributor.authorReventós, Jaume
dc.contributor.authorLópez-López, Rafael
dc.contributor.authorSalvesen, Helga B.
dc.contributor.authorAmant, Frederic
dc.contributor.authorMatias-Guiu, Xavier
dc.contributor.authorMoreno-Bueno, Gema
dc.contributor.authorAbal, Miguel
dc.date.accessioned2015-09-23T10:35:14Z
dc.date.available2015-09-23T10:35:14Z
dc.date.issued2014
dc.identifier.issn1476-4598
dc.identifier.urihttp://hdl.handle.net/10459.1/48742
dc.description.abstractBackground: About 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in high-risk EC patients. Methods: CTC isolation was carried out in peripheral blood samples from 34 patients, ranging from Grade 3 Stage IB to Stage IV carcinomas and recurrences, and 27 healthy controls using two methodologies. Samples were subjected to EpCAM-based immunoisolation using the CELLection™ Epithelial Enrich kit (Invitrogen, Dynal) followed by RTqPCR analysis. The phenotypic determinants of endometrial CTC in terms of pathogenesis, hormone receptor pathways, stem cell markers and epithelial to mesenchymal transition (EMT) drivers were asked. Kruskal-Wallis analysis followed by Dunn’s post-test was used for comparisons between groups. Statistical significance was set at p < 0.05. Results: EpCAM-based immunoisolation positively detected CTC in high-risk endometrial cancer patients. CTC characterization indicated a remarkable plasticity phenotype defined by the expression of the EMT markers ETV5, NOTCH1, SNAI1, TGFB1, ZEB1 and ZEB2. In addition, the expression of ALDH and CD44 pointed to an association with stemness, while the expression of CTNNB1, STS, GDF15, RELA, RUNX1, BRAF and PIK3CA suggested potential therapeutic targets. We further recapitulated the EMT phenotype found in endometrial CTC through the up-regulation of ETV5 in an EC cell line, and validated in an animal model of systemic dissemination the propensity of these CTC in the accomplishment of metastasis. Conclusions: Our results associate the presence of CTC with high-risk EC. Gene-expression profiling characterized a CTC-plasticity phenotype with stemness and EMT features. We finally recapitulated this CTC-phenotype by over-expressing ETV5 in the EC cell line Hec1A and demonstrated an advantage in the promotion of metastasis in an in vivo mouse model of CTC dissemination and homing.ca_ES
dc.description.sponsorshipISCIII PI11/00873; Fundación Asociación Española Contra el Cancer (AECC), Grupos Estables 2011; InveNNta (Innovation in Nanomedicine), co-financed by the European Union (EU) through the Operational Programme for Cross-border Cooperation, Spain-Portugal (POCTEP 2007-2013), European Regional Development Fund (ERDF); Helse Vest, Research Council of Norway, Norwegian Cancer Society and Harald Andersens legat (H.B.S.); L. Alonso-Alconada is recipient of fellowship from the Basque Government (Spain).
dc.language.isoengca_ES
dc.publisherBiomed Centralca_ES
dc.relationMICINN/PN2008-2011/ISCIII PI11/00873
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1186/1476-4598-13-223ca_ES
dc.relation.ispartofMolecular Cancer, 2014, vol. 13, núm. 223, p. 1-10ca_ES
dc.rightscc-by (c) Alonso-Alconada, Lorena et al., 2014ca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectHigh-risk endometrial carcinomasca_ES
dc.subjectCirculating tumor cellsca_ES
dc.subjectEpithelial to mesenchymal transitionca_ES
dc.subject.otherEndometri -- Càncerca_ES
dc.titleMolecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial cancerca_ES
dc.typearticleca_ES
dc.identifier.idgrec023614
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.identifier.doihttps://doi.org/10.1186/1476-4598-13-223


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cc-by (c) Alonso-Alconada, Lorena et al., 2014
Except where otherwise noted, this item's license is described as cc-by (c) Alonso-Alconada, Lorena et al., 2014