Heat stress and thermal ablation induce local expression of nerve growth factor inducible (VGF) in hepatocytes and hepatocellular carcinoma: Preclinical and clinical studies

Scott M. Thompson, Danielle E. Jondal, Kim A. Butters, Bruce E. Knudsen, Jill L. Anderson, Lewis Rowland Roberts, Matthew R Callstrom, David A Woodrum

Research output: Contribution to journalArticle

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Abstract

The purposes of this study were to test the hypothesis that heat stress and hepatic thermal ablation induce nerve growth factor inducible (VGF) and to determine intrahepatic versus systemic VGF expression induced by thermal ablation in vivo and in patients. Hepatocytes and HCC cells were subjected to moderate (45°C) or physiologic (37°C) heat stress for 10 min and assessed for VGF expression at 0-72 h post-heat stress (n 3 experiments). Orthotopic N1S1 HCC-bearing rats were randomized to sham or laser thermal ablation (3 W ´ 90 s), and liver/serum was harvested at 0-7 days postablation for analysis of VGF expression (n 6 per group). Serum was collected from patients undergoing thermal ablation for HCC (n = 16) at baseline, 3-6, and 18-24 h postablation and analyzed for VGF expression. Data were analyzed using ordinary or repeated-measures one-way analysis of variance and post hoc pairwise comparison with Dunnett's test. Moderate heat stress induced time-dependent VGF mRNA (3- to 15-fold; p < 0.04) and protein expression and secretion (3.1- to 3.3-fold; p < 0.05). Thermal ablation induced VGF expression at the hepatic ablation margin at 1 and 3 days postablation but not remote from the ablation zone or distant intrahepatic lobe. There was no detectable serum VGF following hepatic thermal ablation in rats and no increase in serum VGF following HCC thermal ablation in patients at 3-6 and 18-24 h postablation compared to baseline (0.71- and 0.63-fold; p = 0.27 and p = 0.16, respectively). Moderate heat stress induces expression and secretion of VGF in HCC cells and hepatocytes in vitro, and thermal ablation induces local intrahepatic but not distant intrahepatic or systemic VGF expression in vivo.

Original languageEnglish (US)
Pages (from-to)37-47
Number of pages11
JournalGene Expression
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2018

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Nerve Growth Factor
Hepatocytes
Hepatocellular Carcinoma
Hot Temperature
Liver
Serum
Clinical Studies
Laser Therapy
Analysis of Variance

Keywords

  • Heat stress
  • Hepatocellular carcinoma (HCC)
  • Nerve growth factor inducible (VGF)
  • Thermal ablation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Heat stress and thermal ablation induce local expression of nerve growth factor inducible (VGF) in hepatocytes and hepatocellular carcinoma : Preclinical and clinical studies. / Thompson, Scott M.; Jondal, Danielle E.; Butters, Kim A.; Knudsen, Bruce E.; Anderson, Jill L.; Roberts, Lewis Rowland; Callstrom, Matthew R; Woodrum, David A.

In: Gene Expression, Vol. 19, No. 1, 01.01.2018, p. 37-47.

Research output: Contribution to journalArticle

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abstract = "The purposes of this study were to test the hypothesis that heat stress and hepatic thermal ablation induce nerve growth factor inducible (VGF) and to determine intrahepatic versus systemic VGF expression induced by thermal ablation in vivo and in patients. Hepatocytes and HCC cells were subjected to moderate (45°C) or physiologic (37°C) heat stress for 10 min and assessed for VGF expression at 0-72 h post-heat stress (n 3 experiments). Orthotopic N1S1 HCC-bearing rats were randomized to sham or laser thermal ablation (3 W ´ 90 s), and liver/serum was harvested at 0-7 days postablation for analysis of VGF expression (n 6 per group). Serum was collected from patients undergoing thermal ablation for HCC (n = 16) at baseline, 3-6, and 18-24 h postablation and analyzed for VGF expression. Data were analyzed using ordinary or repeated-measures one-way analysis of variance and post hoc pairwise comparison with Dunnett's test. Moderate heat stress induced time-dependent VGF mRNA (3- to 15-fold; p < 0.04) and protein expression and secretion (3.1- to 3.3-fold; p < 0.05). Thermal ablation induced VGF expression at the hepatic ablation margin at 1 and 3 days postablation but not remote from the ablation zone or distant intrahepatic lobe. There was no detectable serum VGF following hepatic thermal ablation in rats and no increase in serum VGF following HCC thermal ablation in patients at 3-6 and 18-24 h postablation compared to baseline (0.71- and 0.63-fold; p = 0.27 and p = 0.16, respectively). Moderate heat stress induces expression and secretion of VGF in HCC cells and hepatocytes in vitro, and thermal ablation induces local intrahepatic but not distant intrahepatic or systemic VGF expression in vivo.",
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