El eje Galectina-8/ALCAM : modulación de las interacciones celulares e implicancias en la progresión del carcinoma mamario

Galectin-8 (Gal-8) is a lectin that recognizes ?-galactosides, which upon secretion functions as a matricellular protein. We have previously demonstrated that ALCAM (CD166) is a Gal-8 ligand. In this thesis, we postulate that Gal-8 - ALCAM heterophilic interactions at the surface of triple negative...

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Detalles Bibliográficos
Autor principal: Ferragut, Fátima Eneida del Valle
Otros Autores: Roguin, Leonor
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2019
Materias:
Galectina-8 (Gal-8)
ALCAM (CD166)
Uniones heterofílicas
Adhesión y migración intercelular
Formación de colonias y esferoides
Tumor murino
N-glicosilación
Sialilación
Ciencias de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2957
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2957.dir/2957.PDF
Aporte de:
Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Galectin-8 (Gal-8) is a lectin that recognizes ?-galactosides, which upon secretion functions as a matricellular protein. We have previously demonstrated that ALCAM (CD166) is a Gal-8 ligand. In this thesis, we postulate that Gal-8 - ALCAM heterophilic interactions at the surface of triple negative MDA-MB-231 human breast cancer cells favour cell adhesion and migration. Our goal focuses on the study of tumorigenic roles mediated by Gal-8 and ALCAM using in vitro and in vivo models. In human breast tissues, Gal-8 and ALCAM are concomitantly expressed, and ALCAM is found increased in the cytoplasm along with tumor progression. At the cell surface, Gal-8 ? ALCAM interactions promoted cell adhesion and migration. Gal-8 or ALCAM silencing diminished cell-cell adhesion. ALCAM showed anti-apoptotic effects, supporting colony and spheroid formation. Dual silencing of Gal-8 and ALCAM delayed tumor growth in a murine model of triple negative breast cancer. Studies on ALCAM N-glycosylation profiles showed abundant permissive structures for Gal-8 binding. Moreover, cell sialylation and ALCAM sialylation inhibited cell adhesion onto Gal-8-coated surfaces. In conclusion, we demonstrate important roles of the Gal-8/ALCAM axis in the progression of triple negative breast cancer.

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