Abstract 1111: Hypoxia inducible factor regulation of galectin3 expression in neuroblastoma cells:Implications in controlling malignant phenotype of neuroblastoma cells

Abstract

Abstract Neuroblastoma (NB) is an extra cranial tumor arising from neural crest progenitor cells. Effective angiogenesis, or new blood vessel formation, is critical for NB tumor growth and progression. Elevated levels of galectin-3 (Gal-3), an angiogenic cytokine is extensively correlated with the malignant behavior and poor prognosis of many cancers. Our studies have shown that Gal-3 expression is significantly up-regulated in aggressive NB cells, and Gal-3 promotes angiogenesis and migration of microglial cells. We have also previously reported that Gal-3 expression is up regulated under low oxygen/hypoxic conditions. The specific mechanisms of Gal-3 induction in NB are not understood. Hypoxic microenvironment drives malignant phenotypes of cancer cells through the transcription factor hypoxia-inducible factor (HIF1). Because NB cells reside in a low oxygen environment, we determined if the hypoxic status modulates Gal-3 expression. In this study, we utilized RT-PCR, western blot analysis, immunofluorescence staining, RNA interference and biochemical approaches. The hypoxia-mimetic, cobalt chloride (CoCl2)-treated neuroblastoma Neuro-2a cells showed enhanced levels of HIF 1 protein. In correlation with the increased HIF1 levels, Gal-3 expression was increased at both RNA and protein levels. Silencing of HIF1 expression by small hairpin interfering RNA in Neuro-2a cells blocked hypoxia induced Gal-3 expression indicating that HIF1 regulates Gal-3 expression in NB cells. Down regulation of Gal-3 resulted in decreased levels of the angiogenic factors IL-6 and urokinase plasminogen activator in association with decreased proliferation, migration, and angiogenesis. Thus our data suggest that HIF1alpha plays a role in the regulation of Gal-3 expression and malignant phenotype of NB cells. Note: This abstract was not presented at the meeting. Citation Format: Umadevi V. Wesley, Esat Resad, Robert J. Dempsey. Hypoxia inducible factor regulation of galectin3 expression in neuroblastoma cells:Implications in controlling malignant phenotype of neuroblastoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1111. doi:10.1158/1538-7445.AM2014-1111