Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/120582
Title: HEPATOCYTE GROWTH FACTOR IS A MAJOR CYTOKINE FOR NSC HOMING TO GLIOMA
Authors: HUANG SIHUA
Keywords: NSC, neural stem cells; HGF, hepatocyte growth factor; VEGF, vascular endothelial growth factor; IL-6, interleukin 6
Issue Date: 20-Jan-2015
Source: HUANG SIHUA (2015-01-20). HEPATOCYTE GROWTH FACTOR IS A MAJOR CYTOKINE FOR NSC HOMING TO GLIOMA. ScholarBank@NUS Repository.
Abstract: Neural stem cell (NSC) homing to brain tumor has been exploited for targeted gene therapy, but the underlying mechanism remains unclear. Various signals were proposed by the literature. We hypothesize that among the 9 known signals we chose from the literature, there would be a major homing signal regulating NSC homing to glioma. Our first specific aim is to observe the homing of NSCs towards glioma in vivo and in vitro. Transwell and microfluidic assays are used and homing was confirmed in both assays. Our second specific aim is to determine the major cytokine(s) that regulates NSC glioma tropism among the 9 known cytokines. We screened these 9 factors for up-regulated gene expression in U87 glioma cells relative to non-cancerous astrocytes. Only VEGF, IL6, and HGF were up-regulated in U87 glioma cells, among which HGF showed the highest up-regulation of >400 fold over astrocytes, versus 2 fold for VEGF and 10 fold for IL6. Similar trends were observed in protein expression measured by ELISA. In transwell assays, HGF induced significant NSC migration relative to VEGF and IL6. Through FACS experiment we also found that NSCs have the highest expression of HGF receptor over the receptors for VEGF and IL6. Our third specific aim is to further explore the role HGF plays in NSC homing to glioma. We found that blocking HGF receptor inhibited NSC migration towards glioma conditioned medium. In live imaging, NSCs migrated along HGF gradient. We conclude that HGF is a major chemoattractant in NSC homing to glioma.
URI: http://scholarbank.nus.edu.sg/handle/10635/120582
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