HYALURONAN INHIBITION IMPROVES PACLITAXEL EFFICACY IN A LUNG CANCER MODEL IN VIVO

FLAVIA PICCIONI; MARIEL FUSCO; MARCO AURELIO DIAZ GUTIERREZ; PAMELA RIBATTO; PAULA ROSELLO; JUAN BAYO; MANGLIO RIZZO; MARIANA MALVICINI

Congreso; Reunion Anual de Biociencias 2022; 2022

Patients with non-small cell lung cancer (NSCLC) progress after treatment with conventional chemotherapy. Cancer stem cells (CSC), a subpopulation in tumor microenvironment (TME), form residual cellular niches and have a key role in resistance and recurrence. CSC express CD133, CD44, ALDH1 and SOX2, among other markers and factors. Hyaluronan (HA), a TME glycosaminoglycan, promotes CSC’ function. We showed that coumarin 4-Methylumbelliferone (4Mu), reduced HA expression in murine Lewis Lung Carcinoma (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 induced the expression of HA-synthases genes HAS2 and HAS3. We aim to investigate a possible link between Pa treatment and the increase in HA metabolism and to evaluate the effect of Pa + 4Mu in vivo. We performed a bioinformatic analysis to find other molecules involved in HA-metabolism and CSC in tumors using TCGA Lung Cancer database. The analysis revealed that ABCC5 is differentially expressed in tumors compared with normal adjacent tissue (p