ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer
Devis Jauregui, Laura (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martinez-Garcia, Elena (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Moiola, Cristian Pablo (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Quiles, Maria Teresa (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Arbós i Via, Maria Antònia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Stirbat, Tomita Vasilica (Institut Curie)
Brochard-Wyart, Françoise (Institut Curie)
García, Ángel (Hospital Universitari Vall d'Hebron)
Alonso-Alconada, Lorena (Centro de Investigación Biomédica en Red de Cáncer)
Abal Posada, Miguel (Centro de Investigación Biomédica en Red de Cáncer)
Díaz-Feijoo, Berta (Hospital Universitari Vall d'Hebron)
Thomas, William (Department of Natural Sciences, Colby-Sawyer College, New London, New Hampshire, United States of America)
Dufour, Sylvie (Present address: Université Paris Est, Faculté de Médecine, Créteil, France, INSERM, U955, Equipe 6, Créteil, France)
Mancebo, Gemma (Hospital del Mar (Barcelona, Catalunya))
Alameda, Francesc (Hospital del Mar (Barcelona, Catalunya))
Reventos, Jaume (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gil-Moreno, Antonio 1965- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Colás Ortega, Eva (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	Endometrial cancer (EC) is the sixth deadliest cancer in women. The depth of myometrial invasion is one of the most important prognostic factors, being directly associated with tumor recurrence and mortality. In this study, ALCAM, a previously described marker of EC recurrence, was studied by immunohistochemistry at the superficial and the invasive tumor areas from 116 EC patients with different degree of myometrial invasion and related to a set of relevant epithelial and mesenchymal markers. ALCAM expression presented a heterogeneous functionality depending on its localization, it correlated with epithelial markers (E-cadherin/β-catenin) at the superficial area, and with mesenchymal markers at the invasive front (COX-2, SNAIL, ETV5, and MMP-9). At the invasive front, ALCAM-negativity was an independent marker of myometrial invasion. This negativity, together with an increase of soluble ALCAM in uterine aspirates from patients with an invasive EC, and its positive correlation with MMP-9 levels, suggested that ALCAM shedding by MMP-9 occurs at the invasive front. In vivo and in vitro models of invasive EC were generated by ETV5-overexpression. In those, we demonstrated that ALCAM shedding was related to a more invasive pattern and that full-ALCAM recovery reverted most of the ETV5-cells mesenchymal abilities, partially through a p-ERK dependent-manner.
Grants:	Instituto de Salud Carlos III PI14-02043 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR-1330
Note:	Altres ajuts: This work was coffinanced by by the European Regional Development Fund (ERDF), and was also supported by the AECC (Grupos Estables de Investigacion 2011-AECC-GCB 110333 REVE), the Fundació La Marató TV3 (2/C/2013), A PERIS grant was awarded to Dr Colas.
Note:	Altres ajuts: MISSSI/RD12-0036-0035
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	ALCAM ; Endometrial cancer ; Myometrial invasion ; MMP-9 ; ETV5
Published in:	Oncotarget, Vol. 9 (march 2018) , p. 16648-16664, ISSN 1949-2553

DOI: 10.18632/oncotarget.24625
PMID: 29682175

17 p, 4.8 MB

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