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.

FERRAGUT, FÁTIMA; COLOMBO, LUCAS L.; SANCHEZ TERRERO, CLARA; VACHETTA, VANINA; WOLFENSTEIN-TODEL, CARLOTA; TRONCOSO, MARÍA F.; RABINOVICH, GABRIEL A.; ELOLA, MARÍA TERESA

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias - LXII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica.; 2017

SOCIEDAD ARGENTINA DE INVESTIGACION CLINICA

Abstract: 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 functions as a cell-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 to immovilized Gal-8 was significantly reduced after ALCAM silencing in MDA-shALCAM (0.13±0.015) and MDA-shALCAM-shGal8 (0.13±0.011) as compared to MDA-shControl cells (0.18±0.019), p0.001. In wound-healing assays onto immovilized Gal-8, migration was significantly reduced after ALCAM silencing in MDA-shALCAM (23.2±1.272) and MDA-shALCAM-shGal8 (22.82±1.173) as compared to MDA-shControl cells (40.88±2.507), p0.001. ALCAM down-regulation, but not Gal-8 silencing, significantly reduced cell proliferation (MDA-shALCAM: 0.39±0.199 and MDA-shALCAM-shGal8: 0.38±0.035 versus MDA-shControl cells: 0.48±0.318, p0.001) and spheroid formation capacity. 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 (291.21±89.778) showed smaller volume than those from MDA-shALCAM cells (1075.79±388.935), 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.Keywords: Galectin-8, ALCAM, breast cancer