FGF19 functions as autocrine growth factor for hepatoblastoma
David J. Elzi1, Meihua Song1, Barron Blackman1, Susan T. Weintraub2, Dolores López-Terrada5, Yidong Chen1,3, Gail E. Tomlinson1,4 and Yuzuru Shiio1,2
1 Greehey Children’s Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, USA
2 Department of Biochemistry, The University of Texas Health Science Center, San Antonio, Texas, USA
3 Department of Epidemiology and Biostatistics, The University of Texas Health Science Center, San Antonio, Texas, USA
4 Department of Pediatrics, The University of Texas Health Science Center, San Antonio, Texas, USA
5 Department of Pathology and Pediatrics, Texas Children’s Hospital and Baylor College of Medicine, Houston, Texas, USA
Correspondence:
Yuzuru Shiio, email:
Keywords: cytokine, FGF19, hepatoblastoma, proteomics, secretome
Received: January 28, 2016 Accepted: April 04, 2016 Published: April 06, 2016
Abstract
Hepatoblastoma is the most common liver cancer in children, accounting for over 65% of all childhood liver malignancies. Hepatoblastoma is distinct from adult liver cancer in that it is not associated with hepatitis virus infection, cirrhosis, or other underlying liver pathology. The paucity of appropriate cell and animal models has been hampering the mechanistic understanding of hepatoblastoma pathogenesis. Consequently, there is no molecularly targeted therapy for hepatoblastoma.
To gain insight into cytokine signaling in hepatoblastoma, we employed mass spectrometry to analyze the proteins secreted from Hep293TT hepatoblastoma cell line we established and identified the specific secretion of fibroblast growth factor 19 (FGF19), a growth factor for liver cells. We determined that silencing FGF19 by shRNAs or neutralizing secreted FGF19 by anti-FGF19 antibody inhibits the proliferation of hepatoblastoma cells. Furthermore, blocking FGF19 signaling by an FGF receptor kinase inhibitor suppressed hepatoblastoma growth. RNA expression analysis in hepatoblastoma tumors revealed that the high expression of FGF19 signaling pathway components as well as the low expression of FGF19 signaling repression targets correlates with the aggressiveness of the tumors. These results suggest the role of FGF19 as autocrine growth factor for hepatoblastoma.
