2004 Fiscal Year Final Research Report Summary
Studies on effect of hypoxia inducible factor on cell adhesion
| Project/Area Number |
15590263
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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 |
General medical chemistry
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
KANNAGI Reiji Aichi Cancer Center, Department of Molecular Pathology, Program Head, 分子病態学部, 部長 (80161389)
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| Co-Investigator(Kenkyū-buntansha) |
YAOMURA Takaaki Aichi Cancer Center, Department of Molecular Pathology, Research Resident, 分子病態学部, リサーチレジデント
KANAMORI Aiko Aichi Cancer Center, Department of Molecular Pathology, Research Scientist, 分子病態学部, 研究員 (00261173)
TAGUCHI Osamu Aichi Cancer Center, Department of Molecular Pathology, Section Chief, 分子病態学部, 室長 (00142167)
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| Project Period (FY) |
2003 – 2004
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| Keywords | hypoxia inducible factor / cell adhesion molecules / DNA microarray / selectin / integrin / syndecan / fibronectin / endothelial cells |
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| Research Abstract |
Cell adhesion molecules are involved in the pathophysiology of various disorders. Some time ago, we had been engaged with the investigation of functional significance of cell adhesion molecules in malignant disorders. During the study, we had noticed that cells cultured under hypoxic conditions exhibit a strong cell adhesive activity. Response to hypoxic conditions is involved in the pathophysiology of wide variety of disorders other than cancers, such as diabetes, kidney diseases, arteriosclerosis, ischemic heart diseases and organ transplantation. These disorders are known to be closely related also to cell adhesion molecules. In this project we had investigated the mechanism involved in the enhancement of cell adhesion under hypoxic conditions. We investigated gene expression in cultured human cells induced by hypoxic conditions with special reference to cell adhesion molecules and carbohydrate determinants having cell adhesive activity using DNA microarray and RT-PCR techniques. Hy
… More
poxic culture of colon cancer cells induced a marked increase in expression of selectin ligands, the sialyl Lewis x and sialyl Lewis a determinants at the cell surface, and this led to a definite increase in cancer cell adhesion to endothelial E-selectin The transcription of genes for FUT7,ST3O and UGT1,which are all known to be involved in the synthesis of the carbohydrate ligands for E-selectin, was significantly induced in cancer cells by hypoxic culture. In addition, a remarkable induction was detected in the genes for syndecan-4(SDC4) and α5-integrin (ITGA5), the cell adhesion molecules involved in the enhanced adhesion of cancer cells to fibronectin. The transcriptional induction by hypoxia was reproduced in the luciferase reporter assays for these genes, which were significantly suppressed by the ortransfection of a dominant-negative form of HIF. These results indicate that the metabolic shifts of cancer cells partly mediated by HIFs significantly enhance their adhesion to vascular endothelial cells, through both selectin- and integrin-mediated pathways. Less
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