Abstract 2786: Downregulated expression of hepatoma-derived growth factor (HDGF) reduces glioma cancer cell tumor growth and angiogenesis

Abstract

Abstract Hepatoma derived growth factor (HDGF) is a mitogenic growth factor in the progression of human glioma. In this paper, we study the gliomagenesis role of HDGF in syngenic glioma rat model by Lenti-virus sh-HDGF (LV-shHDGF) infection. The tumor inhibition of HDGF depletion in rat glioma C6 cells was measured by MRI scanning. We found all glioma tumors growth after implanting but only HDGF knock down tumors had a significant reduction in the tumor size at the 4th-week MRI-scanning. After tumor volume was quantified on serial brain section, we found a 10-folds of reduction in the tumor size was observed in HDGF knock down tumors than scrambles (p<0.005). By survival analysis, rats with gliomas had a less median survival of 25 days and the HDGF knock down group was still alive from the time point of implanting. According to the pathological analysis, the HDGF knock down tumors presented a significant cell apoptosis and reduction in the Ki67 mitotic index, CD31 angiogenesis index, and ANG-4 that exhibited markedly reduced tumor growth and blood vessel formation than controls. In addition, Western blot analysis showed exogenous HDGF increased the expression of PI3K, phospho-Akt, phospho-FAK, phospho-MDM2, PCNA and transcription factors of Iκ-B, NF-κB, cFos, ANG-4, and HIF-α in a dose-dependent manner; however, these tumorigenesis moleculars were significantly decreased in HDGF knock down cells. We concluded that HDGF is a mitogenic growth factor in the progression of glioma and it can be a useful therapeutic target for clinical management of glioma in the future. Note: This abstract was not presented at the meeting. Citation Format: Li-Feng Liu, Shu-Shong Hsu, Chih-Hao Chen. Downregulated expression of hepatoma-derived growth factor (HDGF) reduces glioma cancer cell tumor growth and angiogenesis. [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 2786. doi:10.1158/1538-7445.AM2014-2786