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

FLAVIA PICCIONI ; MARCO AURELIO DÍAZ GUTIERREZ; MARIEL FUSCO; LUCÍA VICTORIA; LUDMILA GARCÍA; MANGLIO MIGUEL RIZZO; MARIANA MALVICINI

Congreso; Reunion Anual de Biociencias 2023; 2023

Sociedad Argentina de Investigacion Clinica

The success of conventional chemotherapy with taxanes employed in patients with non-small cell lung cancer (NSCLC) is restricted at least 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), a glycosaminoglycan of the TME can regulate CSC’s function. We previously 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 LLC cells, the Pa-4Mu combination significantly reduced the tumor volume compared to the Control group (C). In this work, we aimed to validate the effect of 4Mu combined or not with Pa on HA-metabolism and CSC-phenotype gene expression, previously analyzed in vitro in whole (w)LLC cells. We found that Pa increased the expression of CD133 compared to C (p