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 language | English |
|---|---|
| Pages (from-to) | 134-141 |
| Number of pages | 8 |
| Journal | Life Sciences |
| Volume | 200 |
| DOIs | |
| Publication status | Published - May 1 2018 |
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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
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 journal › Article
}
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.
KW - Aged
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 -