| Project/Area Number |
13670163
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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 |
Human pathology
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| Research Institution | Chiba University |
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Principal Investigator |
HARIGAYA Kenichi (2002) Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (40101894)
岸 宏久 (2001) 千葉大学, 大学院・医学研究院, 助手 (90323394)
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| Co-Investigator(Kenkyū-buntansha) |
KITAGAWA Motoo Chiba University, Graduate School of Medicine, Associate professor, 大学院・医学研究院, 助教授 (40262026)
張ケ谷 健一 千葉大学, 大学院・医学研究院, 教授 (40101894)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | TUMOR NECROSIS / TUMOR INVASION / TUMOR METASTASIS / CD44E / VEGF / MICROVESSEL FORMATION / TUMOR PROGRESSION / 腫瘍浸潤転移 / CD44E / 腫瘍のプログレッション / 腫瘍 / 浸潤 / 転移 / バリアント |
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| Research Abstract |
CD44 is a major receptor for hyaluronan and is involved in many biological processes, including cell migration, tumor invasion, and metastasis. To examine how CD44 variant molecules contribute to the tumor cell invasion and metastasis, standard CD44s (82s), CD44v8-10 (82E) and mock (82pCI) transfectants of a CD44-negative human lung cancer cell line were subcutaneously injected into SCID mice. In 82pCI- and 82s-derived tumors, multiple irregular foci of necrosis were prominent, while necrosis was scant in 82E tumors. We found the increased small vessels in the stroma of 82E tumors compared to those of 82s and 82pCI tumors. 82E cells showed the enhanced production of vascular endothelial growth factor (VEGF) in both mRNA and protein levels. The levels of the VEGF mRNA from 82E cells increased in a cell-density dependent manner, and this induced production was abolished by the treatment with hyaluronidase as the cells carried hyaluronan on their surface. Furthermore, the addition of stimulatory anti-CD44 antibody also increased the production of VEGF. These suggest that a homotypic cell-cell contact stimulates the CD44v8-10 through the engagement of cell surface hyaluronan and resulted in the enhanced production of VEGF. Accordingly, our study indicates that CD44v8-10 positive cancer may have an advantage to grow by the induced angiogenesis through the VEGF production.
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