THE GLYCAN-GALECTIN AXIS MODULATES TUMOR DEVELOPMENT AND IMMUNE RESPONSE IN A MURINE MODEL OF COLITIS-ASSOCIATED COLORECTAL CANCER

ALEJANDRO CAGNONI; ANABELA CUTINE; ROSA MORALES; SABRINA GATTO; CRISTIAN MAZZEO; YAMIL MAHMOUD; MARÍA MAY; MARÍA ROMINA GIROTTI; GABRIEL RABINOVICH; KARINA MARIÑO

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAIC, SAI

Inflammatory Bowel Diseases (IBD) have been associated with an increase in the incidence of colorectal cancer (CRC), the third more frequent cancer worldwide. It has been previously reported that the intestinal inflammatory microenvironment favors neoplastic development, although the underlying molecular mechanisms are not yet completely understood. During the last decades, aberrant cell surface glycosylation has been considered an important hallmark of cancer and tumor progression. Glycosylation changes trigger different biological processes via interaction with glycan-binding proteins such as galectins. We aimed to study the effect of the inflammatory microenvironment over the galectin-glycan interactions and CRC progression. We focused our research on the association between intestinal inflammation and neoplastic development with special emphasis in the glycome and its interaction with Galectin-1 and Galectin-4, as they exert important and opposite roles in CRC progression and its metastatic potential. With this purpose, we have established a mouse model of colitis-associated colorectal cancer (CACRC) based on the administration of azoxymethane (AOM) and dextran sulfate sodium (DSS). Wild-type and Galectin-1 KO mice were injected with AOM and then exposed to DSS-containing drinking water. Weight loss, stool consistency and blood were monitored and, after sacrifice, we analyzed number of tumors and tumor size, studied the cellular immune infiltrate and performed immunohistochemical analyses for selected molecules. We found that Galectin-1-lacking mice develop an improved immune response against the tumors, with an increase in activated CD4+ (p=0,03) and CD8+ (p=0,03) T cells. These changes are not related to DSS-induced inflammation, as its administration without AOM does not alter any of these parameters. We also carried out a meta-analysis of transcriptomic data for mouse models of sporadic CRC (sCRC) and CACRC. Metadata analysis showed differential glycogene expression profiles between sCRC and CACRC, indicating a potential influence of intestinal inflammation in aberrant glycosylation profiles.