| Project/Area Number |
11557087
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General surgery
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| Research Institution | Tazuke Kofukai Medical Research Institute |
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Principal Investigator |
ISHIDA Hisao (2000-2001) Tazuke Kofukai Medical reserch Insutitute Dep. V of Oncology, 医学研究所・第5研究部, 研究員 (40322771)
足立 匡司 (1999) 財団法人 田附興風会, 医学研究所・第5研究部, 研究員 (20291015)
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| Co-Investigator(Kenkyū-buntansha) |
TAKI Toshihiko Tazuke Kofukai Medical reserch Insutitute Dep. V of Oncology, 第5研究部, 主幹 (60135605)
MIYAKE Masayuki Tazuke Kofukai Medical reserch Insutitute Dep. V of Oncology, 第5研究部, 部長 (90250076)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2001: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | AIP / angiogenesis / HUVEC / glycosylation / 糖鎖 / metastasis / 血管新生 / 血管新生因子 |
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| Research Abstract |
The molecular basis of cell motility is obviously highly complex and is believed to be controlled by a number of molecular systems, while angiogenesis is an important biological component of fumor progression. The aims of this study were to systematically investigate the possible involvement of proteins at the, cell surface in controlling cell motility and angiogenesis, and further identify the cell surface molecules involved in malignant tumors. The present study utilized an approach based on the selection of HUVEC, which showed motility. We have addressed this study using functional monoclonal antibodies (MAbs), which inhibit HUVEC motility is probes The monoclonal antibody HM7 3 was established after immunization of mice with HUVEC, and was selected on the basis of its ability to inhibit HUVEC migration in a malrigel transwell penetration assay and tube formation. HM7-3 inhibited augiogenesis using eggs and cornea of rats. cDNA cloning revealed that HM7-3 recognizes a new specific protein structure and we named this protein Angiogenesis Inhibiting Protein (AlP). However, the extent of suppression of angiogenesis of malignant tumors is not directly related to the level of ALP expression. A repIication-deficient adenovirus vector was used for the in vivo transfer of All cDNA. Intratumor injection of an adenovirus vector (rAd-AIP) expressing AlP resulted in no inhibition of tumor angiogenesis. As ALP has several N-glycosyIation sites, the function of ALP may be, in general, highly controlled by N-glycosylation. De-N-glycosyltion of ALP results in the loss of functions. The terminal structure, sialic acid might have an important role on angiogenesis. On the other hand, ALP inhibits angiogenesis of the cornea of the rat, but cannot inhibit angiogenesis of malignant cells. The hypothesis may be considered that ALP may have an effect on angiogenesis of normal cells. The further examination will be necessary for the analysis of the mechanism of ALP.
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