SerpinB3 induces dipeptidyl-peptidase IV/CD26 expression and its metabolic effects in hepatocellular carcinoma

Silvano Fasolato, Elisabetta Trevellin, Mariagrazia Ruvoletto, Marnie Granzotto, Giacomo Zanus, Elisa Boscaro, Enrico Babetto, Liliana Terrin, Maria Alberta Battocchio, Francesco Ciscato, Cristian Turato, Santina Quarta, Umberto Cillo, Patrizia Pontisso, Roberto Vettor

Research output: Contribution to journalArticle

Abstract

AIMS: In hepatocellular carcinoma (HCC), the regulatory protease Dipeptidyl-peptidase IV (DPPIV/CD26), that possesses pro-apoptotic properties, has been found abnormally regulated. The protease inhibitor SerpinB3, exerting anti-apoptotic activity, has also been described to be upregulated, especially in HCCs with poor prognosis. The aim of this study was to investigate the possible relationship between these two molecules in HCC patients and in experimental models.

MATERIALS AND METHODS: DPPIV/CD26 and SerpinB3 expression was measured in liver specimens of 67 patients with HCC. HepG2 and Huh7 cells, stably transfected to overexpress SerpinB3, and respective control cells were used to assess biological and metabolic modifications of DPPIV/CD26 activity induced by this serpin.

KEY FINDINGS: DPPIV/CD26 and SerpinB3 were localized in the same tumoral areas and both molecules were correlated with the grade of tumor differentiation, with the highest values detected in GI tumors. Cell lines over-expressing SerpinB3 displayed upregulation of DPPIV/CD26, likely as a feedback mechanism, due to the DPPIV/CD26 protease activity inhibition by SerpinB3, as confirmed by the similar behavior induced by the inhibitor Sitagliptin. Moreover, they exhibited lower glycogen storage and higher lipid accumulation, typical effects of DPPIV/CD26.

SIGNIFICANCE: A close connection between SerpinB3 and DPPPIV has been identified, but further studies are required to better understand the mechanism by which these proteins communicate and exert metabolic effects in HCC.

Original languageEnglish
Pages (from-to)134-141
Number of pages8
JournalLife Sciences
Volume200
DOIs
Publication statusPublished - May 1 2018

Fingerprint

Dipeptidyl Peptidase 4
Tumors
Hepatocellular Carcinoma
Peptide Hydrolases
Serpins
Molecules
Protease Inhibitors
Glycogen
Liver
Cells
Feedback
Lipids
Hep G2 Cells
Neoplasms
Proteins
Theoretical Models
Up-Regulation
Cell Line
Sitagliptin Phosphate

Keywords

  • Aged
  • Antigens, Neoplasm/metabolism
  • Carcinoma, Hepatocellular/metabolism
  • Dipeptidyl Peptidase 4/biosynthesis
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glycogen/metabolism
  • Hep G2 Cells
  • Humans
  • Lipid Metabolism/drug effects
  • Liver Neoplasms/metabolism
  • Male
  • Middle Aged
  • Neoplasm Proteins/metabolism
  • Serpins/metabolism
  • Sitagliptin Phosphate/pharmacology

Cite this

Fasolato, S., Trevellin, E., Ruvoletto, M., Granzotto, M., Zanus, G., Boscaro, E., ... Vettor, R. (2018). SerpinB3 induces dipeptidyl-peptidase IV/CD26 expression and its metabolic effects in hepatocellular carcinoma. Life Sciences, 200, 134-141. https://doi.org/10.1016/j.lfs.2018.03.014

SerpinB3 induces dipeptidyl-peptidase IV/CD26 expression and its metabolic effects in hepatocellular carcinoma. / Fasolato, Silvano; Trevellin, Elisabetta; Ruvoletto, Mariagrazia; Granzotto, Marnie; Zanus, Giacomo; Boscaro, Elisa; Babetto, Enrico; Terrin, Liliana; Battocchio, Maria Alberta; Ciscato, Francesco; Turato, Cristian; Quarta, Santina; Cillo, Umberto; Pontisso, Patrizia; Vettor, Roberto.

In: Life Sciences, Vol. 200, 01.05.2018, p. 134-141.

Research output: Contribution to journalArticle

Fasolato, S, Trevellin, E, Ruvoletto, M, Granzotto, M, Zanus, G, Boscaro, E, Babetto, E, Terrin, L, Battocchio, MA, Ciscato, F, Turato, C, Quarta, S, Cillo, U, Pontisso, P & Vettor, R 2018, 'SerpinB3 induces dipeptidyl-peptidase IV/CD26 expression and its metabolic effects in hepatocellular carcinoma', Life Sciences, vol. 200, pp. 134-141. https://doi.org/10.1016/j.lfs.2018.03.014
Fasolato, Silvano ; Trevellin, Elisabetta ; Ruvoletto, Mariagrazia ; Granzotto, Marnie ; Zanus, Giacomo ; Boscaro, Elisa ; Babetto, Enrico ; Terrin, Liliana ; Battocchio, Maria Alberta ; Ciscato, Francesco ; Turato, Cristian ; Quarta, Santina ; Cillo, Umberto ; Pontisso, Patrizia ; Vettor, Roberto. / SerpinB3 induces dipeptidyl-peptidase IV/CD26 expression and its metabolic effects in hepatocellular carcinoma. In: Life Sciences. 2018 ; Vol. 200. pp. 134-141.
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abstract = "AIMS: In hepatocellular carcinoma (HCC), the regulatory protease Dipeptidyl-peptidase IV (DPPIV/CD26), that possesses pro-apoptotic properties, has been found abnormally regulated. The protease inhibitor SerpinB3, exerting anti-apoptotic activity, has also been described to be upregulated, especially in HCCs with poor prognosis. The aim of this study was to investigate the possible relationship between these two molecules in HCC patients and in experimental models.MATERIALS AND METHODS: DPPIV/CD26 and SerpinB3 expression was measured in liver specimens of 67 patients with HCC. HepG2 and Huh7 cells, stably transfected to overexpress SerpinB3, and respective control cells were used to assess biological and metabolic modifications of DPPIV/CD26 activity induced by this serpin.KEY FINDINGS: DPPIV/CD26 and SerpinB3 were localized in the same tumoral areas and both molecules were correlated with the grade of tumor differentiation, with the highest values detected in GI tumors. Cell lines over-expressing SerpinB3 displayed upregulation of DPPIV/CD26, likely as a feedback mechanism, due to the DPPIV/CD26 protease activity inhibition by SerpinB3, as confirmed by the similar behavior induced by the inhibitor Sitagliptin. Moreover, they exhibited lower glycogen storage and higher lipid accumulation, typical effects of DPPIV/CD26.SIGNIFICANCE: A close connection between SerpinB3 and DPPPIV has been identified, but further studies are required to better understand the mechanism by which these proteins communicate and exert metabolic effects in HCC.",
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TY - JOUR

T1 - SerpinB3 induces dipeptidyl-peptidase IV/CD26 expression and its metabolic effects in hepatocellular carcinoma

AU - Fasolato, Silvano

AU - Trevellin, Elisabetta

AU - Ruvoletto, Mariagrazia

AU - Granzotto, Marnie

AU - Zanus, Giacomo

AU - Boscaro, Elisa

AU - Babetto, Enrico

AU - Terrin, Liliana

AU - Battocchio, Maria Alberta

AU - Ciscato, Francesco

AU - Turato, Cristian

AU - Quarta, Santina

AU - Cillo, Umberto

AU - Pontisso, Patrizia

AU - Vettor, Roberto

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - AIMS: In hepatocellular carcinoma (HCC), the regulatory protease Dipeptidyl-peptidase IV (DPPIV/CD26), that possesses pro-apoptotic properties, has been found abnormally regulated. The protease inhibitor SerpinB3, exerting anti-apoptotic activity, has also been described to be upregulated, especially in HCCs with poor prognosis. The aim of this study was to investigate the possible relationship between these two molecules in HCC patients and in experimental models.MATERIALS AND METHODS: DPPIV/CD26 and SerpinB3 expression was measured in liver specimens of 67 patients with HCC. HepG2 and Huh7 cells, stably transfected to overexpress SerpinB3, and respective control cells were used to assess biological and metabolic modifications of DPPIV/CD26 activity induced by this serpin.KEY FINDINGS: DPPIV/CD26 and SerpinB3 were localized in the same tumoral areas and both molecules were correlated with the grade of tumor differentiation, with the highest values detected in GI tumors. Cell lines over-expressing SerpinB3 displayed upregulation of DPPIV/CD26, likely as a feedback mechanism, due to the DPPIV/CD26 protease activity inhibition by SerpinB3, as confirmed by the similar behavior induced by the inhibitor Sitagliptin. Moreover, they exhibited lower glycogen storage and higher lipid accumulation, typical effects of DPPIV/CD26.SIGNIFICANCE: A close connection between SerpinB3 and DPPPIV has been identified, but further studies are required to better understand the mechanism by which these proteins communicate and exert metabolic effects in HCC.

AB - AIMS: In hepatocellular carcinoma (HCC), the regulatory protease Dipeptidyl-peptidase IV (DPPIV/CD26), that possesses pro-apoptotic properties, has been found abnormally regulated. The protease inhibitor SerpinB3, exerting anti-apoptotic activity, has also been described to be upregulated, especially in HCCs with poor prognosis. The aim of this study was to investigate the possible relationship between these two molecules in HCC patients and in experimental models.MATERIALS AND METHODS: DPPIV/CD26 and SerpinB3 expression was measured in liver specimens of 67 patients with HCC. HepG2 and Huh7 cells, stably transfected to overexpress SerpinB3, and respective control cells were used to assess biological and metabolic modifications of DPPIV/CD26 activity induced by this serpin.KEY FINDINGS: DPPIV/CD26 and SerpinB3 were localized in the same tumoral areas and both molecules were correlated with the grade of tumor differentiation, with the highest values detected in GI tumors. Cell lines over-expressing SerpinB3 displayed upregulation of DPPIV/CD26, likely as a feedback mechanism, due to the DPPIV/CD26 protease activity inhibition by SerpinB3, as confirmed by the similar behavior induced by the inhibitor Sitagliptin. Moreover, they exhibited lower glycogen storage and higher lipid accumulation, typical effects of DPPIV/CD26.SIGNIFICANCE: A close connection between SerpinB3 and DPPPIV has been identified, but further studies are required to better understand the mechanism by which these proteins communicate and exert metabolic effects in HCC.

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KW - Antigens, Neoplasm/metabolism

KW - Carcinoma, Hepatocellular/metabolism

KW - Dipeptidyl Peptidase 4/biosynthesis

KW - Female

KW - Gene Expression Regulation, Enzymologic

KW - Gene Expression Regulation, Neoplastic

KW - Glycogen/metabolism

KW - Hep G2 Cells

KW - Humans

KW - Lipid Metabolism/drug effects

KW - Liver Neoplasms/metabolism

KW - Male

KW - Middle Aged

KW - Neoplasm Proteins/metabolism

KW - Serpins/metabolism

KW - Sitagliptin Phosphate/pharmacology

U2 - 10.1016/j.lfs.2018.03.014

DO - 10.1016/j.lfs.2018.03.014

M3 - Article

C2 - 29524519

VL - 200

SP - 134

EP - 141

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

ER -