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Open Access 01-03-2008 | Hepatic and Pancreatic Tumors

A Novel Function of the Receptor for Advanced Glycation End-Products (RAGE) in Association with Tumorigenesis and Tumor Differentiation of HCC

Authors: Kiyokazu Hiwatashi, MD, Shinichi Ueno, MD, PhD, Kazuhiro Abeyama, MD, PhD, Fumitake Kubo, MD, PhD, Masahiko Sakoda, MD, PhD, Ikuro Maruyama, MD, PhD, Masahiro Hamanoue, MD, PhD, Shoji Natsugoe, MD, PhD, Takashi Aikou, MD, PhD

Published in: Annals of Surgical Oncology | Issue 3/2008

Abstract

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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Title: A Novel Function of the Receptor for Advanced Glycation End-Products (RAGE) in Association with Tumorigenesis and Tumor Differentiation of HCC
Authors: Kiyokazu Hiwatashi, MD
Shinichi Ueno, MD, PhD
Kazuhiro Abeyama, MD, PhD
Fumitake Kubo, MD, PhD
Masahiko Sakoda, MD, PhD
Ikuro Maruyama, MD, PhD
Masahiro Hamanoue, MD, PhD
Shoji Natsugoe, MD, PhD
Takashi Aikou, MD, PhD
Publication date: 01-03-2008
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 3/2008
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-007-9698-8

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A Novel Function of the Receptor for Advanced Glycation End-Products (RAGE) in Association with Tumorigenesis and Tumor Differentiation of HCC

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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