CD13: A novel glycan-binding partner of Galectin-1 in liver endothelium

MANZI, MALENA; SARRIAS, LUCIANA; BACIGALUPO, MARÍA L.; CARABIAS, PABLO; WOLFENSTEIN-TODEL, CARLOTA; ELOLA, MARÍA TERESA; RABINOVICH, GABRIEL A.; ESPELT, MARÍA V.; TRONCOSO, MARIA F.

BUENOS AIRES

Simposio; 3rd GLYCOAR SYMPOSIUM; 2019

GLYCOAR

Galectin-1 (Gal1) belongs to a family of β-galactoside-binding proteins. In hepatocellular carcinoma (HCC), Gal1 is up-regulated and associated with poor patient survival. Previously, we elucidated the molecular mechanisms leading to HCC cell dissemination. Recently, we found that hepatocyte-derived Gal1 promotes liver sinusoidal endothelial cell (LSEC) proliferation and migration, suggesting Gal1 contribution to angiogenesis in liver tumors.We hypothesized that Gal1 modulates LSEC biology by its interaction with glycan ligands. As no ligands for Gal1 have been described in liver endothelium, we aimed to identify Gal1-binding partners in human SK-HEP-1 LSECs, using a proteomic approach.Recombinant Gal1 was coupled to Affi-Gel 15 matrix and a SK-HEP-1 cell membrane fraction was applied to the Gal1-affinity column. Gal1-bound proteins were eluted with lactose, subjected to SDS-PAGE and in gel proteolytic digested. Mass spectrometry analysis identified CD13 as a putative Gal1-binding partner (24% sequence coverage). We confirmed CD13 expression in SK-HEP-1 cells by Western blot and Gal1-CD13 colocalization at cell membranes by immunofluorescence.This is the first time that the glycosylated exopeptidase CD13 is described as a ligand for Gal1. CD13 expression is increased in endothelial cells during tumor-related angiogenesis. These results encourage us to study the relevance of Gal1-CD13 interaction for angiogenesis during liver tumor progression.