Abstract 3105: 4-Methylumbelliferone (4Mu) turns CD133+ lung cancer stem cells (CSCs) more susceptible to conventional chemotherapy

Non-small cell lung cancer (NSCLC) is the most common cause of cancer death worldwide. Taxane-platin chemotherapy is widely used for NSCLC treatment; however, the majority of patients will ultimately 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. A small group of tumor cells called cancer stem cells (CSCs) that express some markers such as CD133, CD44 and ALHD1 have particularly different proliferative, differentiation and self-renewal potential. In fact, CD133+ NSCLC cells showed significantly higher abilities of self-renewal and drug resistance characteristics when compared to CD133- cells. It has been partly described how the TME component hyaluronan (HA) regulates CSCs function. We have previously demonstrated that 4-Methylumbelliferone (4Mu), a modulator of HA synthesis, reduces CSCs properties in hepatocarcinoma. Here, we observed that HA was present Lewis Lung Carcinoma (LLC) tumors from mice. We found HA+ LLC cells; thus cancer cells produced, at least in part, the HA observed in tumors. We also 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