ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer

Laura Devis, Elena Martinez-Garcia, Cristian P. Moiola, Maria Teresa Quiles, Maria Antonia Arbos, Tomita Vasilica Stirbat, Françoise Brochard-Wyart, Ángel García, Lorena Alonso-Alconada, Miguel Abal, Berta Diaz-Feijoo, William Thomas, Sylvie Dufour, Gemma Mancebo, Francesc Alameda, Jaume Reventos, Antonio Gil-Moreno, Eva Colas

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5 Citations (Scopus)

Abstract

© Devis et al. 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.
Original languageEnglish
Pages (from-to)16648-16664
JournalOncotarget
Volume9
Issue number24
DOIs
Publication statusPublished - 30 Mar 2018

Keywords

  • ALCAM
  • ETV5
  • Endometrial cancer
  • MMP-9
  • Myometrial invasion

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    Devis, L., Martinez-Garcia, E., Moiola, C. P., Quiles, M. T., Arbos, M. A., Stirbat, T. V., Brochard-Wyart, F., García, Á., Alonso-Alconada, L., Abal, M., Diaz-Feijoo, B., Thomas, W., Dufour, S., Mancebo, G., Alameda, F., Reventos, J., Gil-Moreno, A., & Colas, E. (2018). ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer. Oncotarget, 9(24), 16648-16664. https://doi.org/10.18632/oncotarget.24625