Galectin 1 promotes tumor cell migration by enhancing Na+/H+ exchanger isoform 1 (NHE1) activity

BOCANEGRA V; CROCI DO; COSTANTINO VV; GIL LORENZO AF; GARRAMUÑO VALLÉS , P

Mendoza

Congreso; 1st Freiburg - Mendoza Symposium on Translational Medicine Cancer, Cardiovascular and Neurological Maladies; 2018

Universidad Nacional de Cuyo

Tumor cells evade immune responses and shape local and systemic microenvironments establishing a distinctive cellular phenotype. Galectin 1 (Gal1), a glycan-binding protein, controls tumor progression by modulating tumor immunity and migration through binding to specific glycan structures of cell surface receptors. In solid tumors, NHE1 favors cancer progression through pH modulation. We aimed to elucidate the role of Gal1 on NHE1 regulation in murine melanoma cells and its role in tumor cell migration. To determine NHE1 activity we used a BCECF-AM flow cytometry kinetics assay. We observed increased NHE1 activity in melanoma cells in comparison to a non-tumorigenic cell line. To evaluate Gal1 participation in NHE1 hyperactivity, cells were treated with NHE1 inhibitor (Eipa), recombinant Gal1 (rGal1) or were silenced for Gal1 (shGal1). We observed diminished NHE1 activity after Eipa treatment with similar results obtained after shGal1 silencing. Notably, rGal1 treatment augmented NHE1 activity, reverting the Eipa-dependent inhibition of NHE1. Accordingly, Gal1 immunoprecipitated with NHE1, suggesting that Gal1 could interact with NHEI and control pH-dependent regulation by this antiporter. To further address the biological relevance of NHE1/Gal1 interaction, we evaluated migration of shGal1 melanoma cells. Both Gal1 signaling or NHE-1 inhibition impaired B16 cell migration. In contrast, exposure to rGal1 restored tumor migration under both conditions. These results suggest a possible role for Gal1 in modulating tumor cell behavior via NHE1 activation. Understanding the mechanisms through which the acidic microenvironment could shape tumor cell phenotype could help improve anticancer therapies