A Novel Function of the Receptor for Advanced Glycation End-Products (RAGE) in Association with Tumorigenesis and Tumor Differentiation of HCC
Open accessAbstract
BACKGROUND: The expression of the receptor for advanced glycation end products (RAGE) has an impact on the mechanisms giving rise to characteristic features of various cancer cells. The purpose of this study was to elucidate the clinicopathological relevance of the level of RAGE expression in patients with hepatocellular carcinoma (HCC) and to explore the effect of RAGE expression on the characteristic features of HCC. METHODS: The expression of RAGE was assessed in paired cancer and noncancerous tissues with HCC, using reverse-transcription polymerase chain reaction (RT-PCR), and immunohistochemistry. The quantitative RT-PCR data were analyzed in association with the clinicopathological factors of the patients with HCC. In in vitro experiments, the survival of RAGE-transfected Cos7 and mock-transfected Cos7 cells was compared under hypoxic conditions. In addition, after reducing RAGE levels in RAGE-transfected Cos7 cells by siRNA, similar experiments were performed. RESULTS: The expression of RAGE mRNA was lower in normal liver than in hepatitis and highest in HCC. Furthermore, in HCC, it was high in well- and moderately differentiated tumors but declined as tumors dedifferentiated to poorly differentiated HCC. Furthermore, HCC lines resistant to hypoxia were found to have higher levels of RAGE expression, and RAGE transfectant also showed significantly prolonged survival under hypoxia. CONCLUSIONS: Our results suggest that HCC during the early stage of tumorigenesis with less blood supply may acquire resistance to stringent hypoxic milieu by hypoxia-induced RAGE expression.
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RAGE amounts are increased in HCC liver compared with hepatitis and healthy liver, and serum AGE amounts are higher in HCC than in NASH and healthy liver specimens.
“Increased amounts of RAGE are also observed in the liver of hepatocellular carcinoma (HCC), and its level is significantly greater than it is liver affected by hepatitis and healthy liver specimens.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [129]
AGEs and RAGE play an important role in promoting NAFLD, NASH, fibrosis/cirrhosis, and HCC pathogenesis.
“These results suggest an important role for AGEs and RAGE in promoting NAFLD, NASH, fibrosis/cirrhosis, and HCC pathogenesis129–131.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [129]
In HCC, AGE-RAGE interaction is associated with angiogenesis and tumor proliferation and invasion, which are ameliorated by RAGE inhibition.
“In HCC, the AGE-RAGE interaction is associated with angiogenesis and tumor proliferation and invasion, which are ameliorated by RAGE inhibition.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [129]
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- Authors
- Hiwatashi, K., Ueno, S., Abeyama, K., Kubo, F., Sakoda, M., Maruyama, I., Hamanoue, M., Natsugoe, S., & Aikou, T.
- Affiliations
- Kagoshima University (JP)
- Corresponding author
- Ueno, Shinichi
- ORCID
- Maruyama, Ikuro
- Venue
- Annals of Surgical Oncology
- Published
- 2007-12-15
- Volume
- 15
- Issue
- 3
- Pages
- 923-933
- ISSN
- 1068-9265 (ISSN-L)
- 1534-4681
- PMC
- PMC2234441
- OpenAlex
- W2038392396
- Cited by
- 72
- References
- 41
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2021: 9 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 10 · 2014: 5 · 2013: 7 · 2012: 7
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Surgical Oncology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kanazawa University
- Japan Society for the Promotion of Science (16659493, 14370359)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- receptor for advanced glycation end products, RAGE, hepatocellular carcinoma, carcinogenesis, tumor differentiation, hypoxia, hypoxia tolerance, tumor dedifferentiation, clinicopathological correlation, siRNA knockdown
- MeSH terms
- Receptor for Advanced Glycation End Products, Aged, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Receptors, Immunologic, Cell Line, Tumor
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