HYALURONIC ACID-INHIBITION IMPROVESLITAXEL EFFICACY IN A LUNG CANCER MODEL IN VIVO. PAC

PICCIONI, FLAVIA VALERIA; FUSCO, MARIEL; DÍAZ GUTIERREZ, MARCO A; RIBATTO, PAMELA; ROSELLO, PAULA; BAYO, JUAN; RIZZO, MANGLIO; MALVICINI, MARIANA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2022

Sociedad Argentina de Investigación Clínica

Patients with non-small cell lung cancer (NSCLC) progress aftertreatment with conventional chemotherapy. Cancer stem cells(CSC), a subpopulation in tumor microenvironment (TME), formresidual cellular niches and have a key role in resistance and recurrence.CSC express CD133, CD44, ALDH1 and SOX2, amongother markers and factors. Hyaluronan (HA), a TME glycosaminoglycan,promotes CSC’ function. We showed that coumarin 4-Methylumbelliferone(4Mu), reduced HA expression in murine Lewis LungCarcinoma (LLC) cells and increased sensibility to paclitaxel (Pa),reducing the clonogenic and tumor-forming ability of LLC CD133+treated with Pa in vitro. We also observed that Pa treatment inducedthe expression of HA-synthases genes HAS2 and HAS3. We aim toinvestigate a possible link between Pa treatment and the increase inHA metabolism and to evaluate the effect of Pa + 4Mu in vivo. Weperformed a bioinformatic analysis to find other molecules involvedin HA-metabolism and CSC in tumors using TCGA Lung Cancer database.The analysis revealed that ABCC5 is differentially expressedin tumors compared with normal adjacent tissue (p