IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Down-regulation of Galectin-8 and its ligand ALCAM (?activated leukocyte cell adhesion molecule?, CD166) reduces in vivo tumor growth in a murine model of breast cancer.
Autor/es:
FERRAGUT F; VACHETTA VS; RABINOVICH GA; TERRERO CL; TRONCOSO MF; COLOMBO L; WOFENSTEIN-TODEL, C; ELOLA MT
Lugar:
Ciudad de Buenos Aires
Reunión:
Congreso; Reunión Conjunta de Sociedades Biomédicas; 2017
Resumen:
Galectin-8 (Gal-8) is a ?tandem-repeat?-type galectin, with two carbohydrate recognition domains. We previously showed that the activated leukocyte cell adhesion molecule (ALCAM), which is a cell adhesion molecule, serves as a Gal-8 ligand. The aims of this work were: 1) To analyze cell surface effects of the Gal-8/ALCAM axis on adhesion and migration of human MDA-MB-231 breast cancer cells; 2) To investigate Gal-8 and ALCAM effects on cell proliferation and spheroid formation; 3) To evaluate Gal-8 and ALCAM effects in a murine model of breast cancer. We established MDA-MB-231 cell lines in which Gal-8 (MDA-shGal8) and/or ALCAM expression (MDA-shALCAM) were stably knocked-down with specific shRNA; scrambled-shRNA was used for controls (MDA-shControl). Our results showed that cell adhesion onto immobilized Gal-8 was significantly reduced after ALCAM silencing in MDA-shALCAM (26.3±7.0%) and MDA-shALCAM-shGal8 (25.6±6.8%) as compared to MDA-shControl cells (100%), p0.05. In migration assays onto immobilized Gal-8, wound-closure percentages were significantly reduced after ALCAM silencing in MDA-shALCAM (23.2±1.3%) and MDA-shALCAM-shGal8 (22.8±1.2%) as compared to MDA-shControl cells (40.8±2.5%), p0.001. ALCAM down-regulation, but not Gal-8 silencing, significantly reduced cell proliferation by MTT (MDA-shALCAM: 0.39±0.19 and MDA-shALCAM-shGal8: 0.38±0.03 versus MDA-shControl cells: 0.48±0.31, p0.001) and spheroid volume (80%, p0.001). Tumor growth in nude mice indicated that MDA-shControl tumors were significantly larger than those generated by MDA-shALCAM and by MDA-shGal8 cells (p0.05); tumors derived from MDA-shALCAM-shGal8 (291.2±89.8) showed smaller volume than those from MDA-shALCAM cells (1075.8±388.9), p0.05 at 90 days post-inoculum. Our results demonstrate that there are ALCAM-Gal-8 glycan-dependent interactions at the cell surface, and that depletion of Gal-8 and ALCAM delays primary tumor growth affecting breast cancer progression.