Hyaluronan modulation by 4-Methylumbelliferone (4Mu) confers chemo sensibility to lung cancer stem cells

DÍAZ, MA; BEZAZIAN, A; ESCRIBANO, A; FUSCO, M

Congreso; Reunión anual de sociedades de Biociencia; 2020

Sociedad Argentina de Investigación Clínica

Taxane-platin chemotherapy is widely used for non-small cell lung cancer (NSCLC). However, the majority of patients will progress or relapse. In the tumor microenvironment (TME) cancer cells co-exist with cellular and non-cellular components that drive tumor processes such as chemotherapy resistance. Cancer stem cells (CSCs) are tumor initiating cells identified by CD133, CD44 and ALDH1 among others markers, which form residual niches involved in tumor recurrence. It has been partly described how the TME hyaluronan (HA) regulates CSCs function. We have demonstrated that 4-Methylumbelliferone (4Mu), a modulator of HA synthesis, reduces CSCs properties in hepatocarcinoma. Here, we observed that HA was present on mice Lewis Lung Carcinoma (LLC) tumors. We found HA+ LLC cells; thus cancer cells produced, at least in part, the HA observed in tumors. We observed about 6.58 ± 0.83 % of CD133+ CSCs on in vitro cultured LLC cells. Isolated CD133+ cells showed higher expression of HA and CD44 in comparison with non-CSCs population (p