ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer
Autor/a
Devis, Laura
Martinez-Garcia, Elena
Moiola, Cristian P.
Quiles Pérez, María Teresa
Arbós Vilà, Maria Antonia
Vasilica Stirbat, Tomita
Brochard-Wyart, Françoise
García, Ángel
Alonso-Alconada, Lorena
Abal, Miguel
Diaz-Feijoo, Berta
Thomas, William
Dufour, Sylvie
Mancebo, Gemma
Alameda, Francesc
Reventós, Jaume
Gil-Moreno, Antonio
Colas, Eva
Fecha de publicación
2018-03-30ISSN
1949-2553
Resumen
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.
Tipo de documento
Artículo
Versión del documento
Versión aceptada
Lengua
English
Materias (CDU)
61 - Medicina
Palabras clave
Endometri--Càncer
Citoplasma
Tumors
Endometrio--Cáncer
Citogenética
Tumores
Endometriosis--Cancer
Myometrium
Cytoplasm
Tumors
Páginas
17
Publicado por
Impact Journals
Colección
9; 24
Publicado en
Oncotarget
Citación
Devis, Laura; Martinez-Garcia, Elena; Moiola, Cristian P. [et al.]. ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer. Oncotarget, 2018, vol. 9, núm. 24, p. 16648-16664. Disponible en: <http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=24625&path[]=77263>. Fecha de acceso: 28 dic. 2019. DOI: 10.18632/oncotarget.24625.
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Derechos
Devis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Excepto si se señala otra cosa, la licencia del ítem se describe como https://creativecommons.org/licenses/by/3.0/