CHANGES IN CSCs PHENOTYPE PROMOTED BY GLYCOSAMINGLYCANS MODULATION IMPROVES PACLITAXEL- RESPONSE IN LUNG CANCER

PICCIONI, FLAVIA VALERIA; DÍAZ GUTIERREZ, MARCO A; FUSCO, MARIEL; VICTORIA, LUCÍA; GARCÍA, MARÍA LUDMILA; ROSELLO, PAULA; RIZZO, MANGLIO; MALVICINI MARIANA

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

Sociedad Argentina de Investigación Clínica

The success of conventional chemotherapy with taxanes employedin patients with non-small cell lung cancer (NSCLC) is restricted atleast in part by cancer stem cell (CSC)-niches within the tumor microenvironment(TME). These cells express CD133, CD44, CD47,and SOX2, among other markers and factors. Hyaluronan (HA), aglycosaminoglycan of the TME can regulate CSC’s function. Wepreviously demonstrated that coumarin 4-Methylumbelliferone(4Mu) reduced HA expression in murine Lewis Lung Carcinoma(LLC) cells and increased their sensibility to paclitaxel (Pa) in vitro.Also, CD133+ cells differentially expressed HA compared to CD133-cells. In a mice model generated by subcutaneous injection of LLCcells, the Pa-4Mu combination significantly reduced the tumor volumecompared to the Control group (C). In this work, we aimed tovalidate the effect of 4Mu combined or not with Pa on HA-metabolismand CSC-phenotype gene expression, previously analyzed invitro in whole (w)LLC cells. We found that Pa increased the expressionof CD133 compared to C (p