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Different Glucose Uptake and Glycolytic Mechanisms Between Hepatocellular Carcinoma and Intrahepatic Mass-Forming Cholangiocarcinoma with Increased 18F-FDG Uptake

 Jong Doo Lee  ;  Woo Ick Yang  ;  Young Nyun Park  ;  Kyung Sik Kim  ;  Jin Sub Choi  ;  Mijin Yun  ;  Dooheun Ko  ;  Tae-Sung Kim  ;  Arthur E.H. Cho  ;  Hye Mi Kim  ;  Kwang-Hyub Han  ;  Seung-Soon Im  ;  Yong-Ho Ahn  ;  Chang Woon Choi  ;  Jeon Han Park 
 JOURNAL OF NUCLEAR MEDICINE, Vol.46(10) : 1753-1759, 2005 
Journal Title
Issue Date
Bile Duct Neoplasms/diagnostic imaging ; Bile Duct Neoplasms/metabolism ; Bile Ducts, Intrahepatic/diagnostic imaging ; Bile Ducts, Intrahepatic/metabolism ; Carcinoma, Hepatocellular/diagnostic imaging* ; Carcinoma, Hepatocellular/metabolism* ; Cholangiocarcinoma/diagnostic imaging* ; Cholangiocarcinoma/metabolism* ; Fluorodeoxyglucose F18/pharmacokinetics* ; Glucose/pharmacokinetics* ; Glycolysis ; Humans ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/pharmacokinetics ; Tumor Cells, Cultured
(18)F-FDG uptake in malignant tumors largely depends on the presence of facilitated glucose transporters, especially type 1 (Glut 1) and a rate-limiting glycolytic enzyme, hexokinase (HK) type II. Low expression of Glut 1 was reported in hepatocellular carcinoma (HCC), whereas high expression was found in cholangiocarcinoma. Immunohistochemistry and proteome analysis were performed to obtain a detailed evaluation of the mechanisms involved in glucose uptake and use in these tumors. METHODS: Tumor tissues obtained from both HCC (n = 7) and mass-forming cholangiocarcinoma patients (n = 7) who showed increased (18)F-FDG uptake on PET were used. Immunohistochemistry for Glut 1 and HK I-III was performed in all tumor tissues. To identify proteins that regulate carbohydrate metabolism, a proteome analysis with matrix-assisted laser desorption ionization-time of flight and enzymatic digestion in-gel were performed using 8 available tumor samples and 3 normal liver tissues. Of the 8 tumor samples, 4 were HCCs; one was an intermediate phenotype HCC, and 3 were cholangiocarcinomas. The spot intensity of the proteins was calculated using proteome data; the tissues then were divided into 2 groups on the basis of the protein expression pattern, because the protein expression pattern of the intermediate-phenotype HCC was close to that of the cholangiocarcinomas. Group A included the HCCs and group B included the intermediate-phenotype HCC as well as the cholangiocarcinomas. RESULTS: Immunoreactivity for Glut 1 was positive in all cholangiocarcinomas, but was negative in all HCCs except the one intermediate phenotype. However, HK II was positive in HCCs but was negative in 6 of the 7 cholangiocarcinomas. A total of 331 protein spots with a P value of <0.05 were identified by proteome analysis. Thirteen of these proteins that regulate carbohydrate metabolism were selected. The pentose phosphate pathway was increased in both groups, but more significantly in group B. Gluconeogenesis enzymes were decreased in both groups, but the tricarboxylic acid cycle-regulating enzyme expression was variable. CONCLUSION: HCCs have different glucose-regulating mechanisms from those of cholangiocarcinomas, even though both tumors showed increased (18)F-FDG uptake on PET scans. Further studies are required with regard to energy metabolism and (18)F-FDG uptake patterns in association with various oncogenic alterations regulating multiple steps of the glycolytic pathways.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sik(김경식) ORCID logo https://orcid.org/0000-0001-9498-284X
Kim, Hye Mi(김혜미)
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
Yun, Mi Jin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
Lee, Jong Doo(이종두)
Im, Seung Soon(임승순)
Cho, Arthur Eung Hyuck(조응혁) ORCID logo https://orcid.org/0000-0001-8670-2473
Choi, Jin Sub(최진섭)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
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