TY - JOUR
T1 - ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer
AU - Devis, Laura
AU - Martinez-Garcia, Elena
AU - Moiola, Cristian P.
AU - Quiles, Maria Teresa
AU - Arbos, Maria Antonia
AU - Stirbat, Tomita Vasilica
AU - Brochard-Wyart, Françoise
AU - García, Ángel
AU - Alonso-Alconada, Lorena
AU - Abal, Miguel
AU - Diaz-Feijoo, Berta
AU - Thomas, William
AU - Dufour, Sylvie
AU - Mancebo, Gemma
AU - Alameda, Francesc
AU - Reventos, Jaume
AU - Gil-Moreno, Antonio
AU - Colas, Eva
N1 - Publisher Copyright:
© Devis et al.
PY - 2018/3/30
Y1 - 2018/3/30
N2 - 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.
AB - 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.
KW - ALCAM
KW - ETV5
KW - Endometrial cancer
KW - MMP-9
KW - Myometrial invasion
UR - http://www.scopus.com/inward/record.url?scp=85044762205&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.24625
DO - 10.18632/oncotarget.24625
M3 - Article
AN - SCOPUS:85044762205
SN - 1949-2553
VL - 9
SP - 16648
EP - 16664
JO - Oncotarget
JF - Oncotarget
IS - 24
ER -