PDTM-37. GALECTIN-3 PROMOTES CXCR2 EXPRESSION IN MEDULLOBLASTOMA

Abstract

Abstract Brain tumors are the leading cause of childhood cancer mortality, with medulloblastoma (MB) representing the most frequent malignant tumor. The identification of cancer stem cell (CSC) populations in MB has play a vital role in drug resistance, and cancer relapse. Galectin-3 (Gal-3) a multifunctional β-galactoside-binding protein is known to participate in tumor progression and drug resistance. However, the exact role of Gal-3 in medulloblastoma tumor pathophysiology is yet unknown. In this study, we observed higher levels of stem/progenitor cell markers, such as Oct4, Sox2, CD133 and Nanog in MB slices. Among the Gal family, Gal-3 in particular was highly expressed in MB tumor slices. To further investigate Gal-3’s role in the pathophysiology of MB, we used either small interfering RNA (siRNA) to knock down Gal-3 expression or Gal-3 inhibitor, TD139 to suppress Gal-3 expression in ex vivo slice culture model. Upon suppressing Gal-3 in parental MB slices, drug resistance (MDR1and MPR1) and stem cell related gene expression were all significantly decreased. Furthermore, CXCL6, CXCL7 and CXCR2 were down-regulated in Gal-3-knockdown or Gal-3 inhibitor treated MB tumor slices, while CXCR2 overexpression in Gal-3-knockdown or Gal-3 inhibitor treated MB slices restored their viability. These results indicate that highly expressed Gal-3 may up-regulate CXCR2 to augment MB invasiveness and progression. Gal-3 may be a prognostic and innovative target for the treatment of MB.