2000 Fiscal Year Final Research Report Summary
Analysis of anti-cancer effect for the chemokine SDF-1 and the receptor CXCR4 in gastrointestinal cancer
| Project/Area Number |
11671251
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KENJI Shibuta Medical Institute of Bioregulation Kyushu Univ.Research Associate, 生体防御医学研究所, 助手 (70253531)
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| Co-Investigator(Kenkyū-buntansha) |
SADANAGA Noriaki Medical Institute of Bioregulation Kyushu Univ.Research Associate, 生体防御医学研究所, 助手 (20304826)
MORI Masaki Medical Institute of Bioregulation Kyushu Univ.Professor, 生体防御医学研究所, 教授 (70190999)
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| Project Period (FY) |
1999 – 2000
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| Keywords | gastrointestinal cancer / hepatoma / CXC chemokine / SDF-1 / CXCR4 / RT-PCR |
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| Research Abstract |
We have recently demonstrated on Northern blots analysis and reverse transcription-polymerase chain reaction (RT-PCR) that expression of the a-chemokine hIRH/SDF-1a mRNA was reduced in human hepatocellular carcinoma, digestive tract cancers such as esophageal cancer, gastric cancer and colon cancer, human malignant cell lines and colonic premalignant polyp although its expression is common in human normal tissues. Furthermore, there are no more than our two reports on the mRNA status of a-chemokine receptor CXCR4, whose ligand is hIRH/SDF-1a, in human cancers. The present study was designed to analyze the expression of CXCR4 mRNA by RT-PCR and to investigate the distribution of SDF-1a/CXCR4 proteins expression in hepatocellular carcinoma, adjacent normal liver tissue and human malignant cell lines by the immunochemical staining. Although CXCR4 mRNA was expressed widely on human almost normal organs and maligmant cell lines, the expression in the majority of hepatoma was reduced compared with that in adjacent non-cancer tissue. There was a significant correlation in the intensity of mRNA expression between CXCR4 and its ligand hIRH/SDF-1. Furthermore, the immunochemical staining in vivo and in vitro showed that CXCR4 was expressed on varing intracellular molecules such as the nuclear surface, the intranucleus and the cytoplasm. Particularly, CXCR4 expression in cytoplasm was definitely limited to the hepatocells around the central vein, and is constitutively consistent with that of SDF-1a. Based on these facts, the CXCR4/SDF-1 interaction possibly plays an important role of liver carcinogenesis in vivo.
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