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dc.contributor.authorAlonso-Alconada, Lorenaen_US
dc.contributor.authorMuinelo-Romay, Lauraen_US
dc.contributor.authorMadissoo, Kadrien_US
dc.contributor.authorDiaz-Lopez, Antonioen_US
dc.contributor.authorKrakstad, Camillaen_US
dc.contributor.authorTrovik, Joneen_US
dc.contributor.authorWik, Elisabethen_US
dc.contributor.authorHapangama, Dharanien_US
dc.contributor.authorCoenegrachts, Lieveen_US
dc.contributor.authorCano, Amparoen_US
dc.contributor.authorGil-Moreno, Antonioen_US
dc.contributor.authorChiva, Luisen_US
dc.contributor.authorCueva, Juanen_US
dc.contributor.authorVieito, Mariaen_US
dc.contributor.authorOrtega, Eugeniaen_US
dc.contributor.authorMariscal, Javieren_US
dc.contributor.authorColas, Evaen_US
dc.contributor.authorCastellvi, Josepen_US
dc.contributor.authorCusido, Maiteen_US
dc.contributor.authorDolcet, Xavieren_US
dc.contributor.authorNijman, Hans W.en_US
dc.contributor.authorBosse, Tjallingen_US
dc.contributor.authorGreen, John A.en_US
dc.contributor.authorRomano, Andreaen_US
dc.contributor.authorReventos, Jaumeen_US
dc.contributor.authorLopez-Lopez, Rafaelen_US
dc.contributor.authorSalvesen, Helga Birgitteen_US
dc.contributor.authorAmant, Fredericen_US
dc.contributor.authorMatias-Guiu, Xavieren_US
dc.contributor.authorMoreno-Bueno, Gemaen_US
dc.contributor.authorAbal, Miguelen_US
dc.contributor.authoron behalf of ENITEC Consortiumen_US
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.en_US
dc.publisherBioMed Centraleng
dc.rightsAttribution CC BYeng
dc.subjectHigh-risk endometrial carcinomaseng
dc.subjectCirculating tumor cellseng
dc.subjectEpithelial to mesenchymal transitioneng
dc.subjectStem celleng
dc.titleMolecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial canceren_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright Alonso-Alconada et al.; licensee BioMed Central Ltd.
dc.rights.holderLorena Alonso-Alconada et al.; licensee BioMed Central Ltd.
dc.source.journalMolecular Cancer

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