Coumarin 4-Methylumbelliferone (4Mu) reduces the resistance to conventional chemotherapy and the tumorigenic capability of CD133+ lung cancer cells.

PICCIONI, FLAVIA; GAYET PREISS, FERNANDO; MALVICINI, MARIANA; FUSCO, MARIEL; ROSELLO, PAULA; DIAZ, MARCO AURELIO; RIZZO MANGLIO

Buenos Aires

Congreso; Reunión anual SAIC (Sociedad Argentina de Investigación Clínica) / SAI; 2021

Patients with non-small cell lung cancer (NSCLC) will ultimately progress or relapse after treatment with conventional chemotherapy (Qx) with platinum-taxanes. In the tumor microenvironment (TME) cancer stem cells (CSC), which express CD133, CD44 and CD47 among other markers form residual cell niches involved in the recurrence after treatment. Hyaluronan (HA), a component of the TME, regulates, at least in part, the function of CSCs. We previously demonstrated that tissue sections from murine Lewis Lung Carcinoma (LLC) tumors present high levels of HA and it is higher on isolated LLC CSCs (CD133+) compared with the non-CSCs population (CD133-; by FACS). Our analysis of TCGA data from patients with NSLCS showed that HA Synthase (HAS) 3 expression strongly correlates with levels of transcription factors involved in CSC phenotype. We modulated HA with the coumarin 4Mu, detecting an increase in the sensibility of LLC cells to paclitaxel (Pa). We aimed to cross-validate the TCGA findings on whole LLC and isolated CD133+ cells after exposure to Pa or cisplatin (Cis), alone or in combination with 4Mu. We analyzed the expression of HAS and CSCs genes by qPCR. The expression of HA and their clonogenic and tumor-forming capability was also evaluated. Pa increases mRNA levels of HAS3 (p