| Project/Area Number |
09670041
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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 physiology
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| Research Institution | HAMAMATU UNIVERSITY SCHOOL OF MEDECINE |
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Principal Investigator |
TAKADA Akikazu Hamamatsu Univ. Sch. of Med., Dept. Physiology, Professor, 医学部, 教授 (80092980)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Nobuo Hamamatsu Univ. Sch. of Med., Dept. Physiology, Reseach Associate, 医学部, 助手 (90260281)
IHARA Hayato Hamamatsu Univ. Sch. of Med., Dept. Physiology, Reseach Associate, 医学部, 助手 (00223298)
URANO Tetsumei Hamamatsu Univ. Sch. of Med., Dept. Physiology, Associate Professor, 医学部, 助教授 (50193967)
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| Project Period (FY) |
1997 – 1999
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| Keywords | angiostatin / angiogenesis / tumor metastasis & invasion / plasminogen |
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| Research Abstract |
(1) Recently much attention has been paid to angiogenesis, which appeared to play important roles in tumor growth and its metastasis as well as tissue repair and remodeling. Folkman et al reported that "angiostatin" , a fragment of plasminogen molecule (kringle 1-3), showed strong inhibitory activity toward angiogenesis. Since detailed mechanism for angiostatin to be generated and that to inhibit angiogenesis are not elucidated yet, we tried to identify angiostatin molecule in cancer tissue and to reveal its structural characteristics.
(2) We generated and purified "angiostatin (K1-3) " as an elastase digested fragment of human plasminogen. By this purified angiostatin, two monoclonal antibodies were developed. Both antibodies were shown to react with angiostatin but not with mini-plasminogen which lacks kringle 1-4. These also reacted with plasminogen molecule.
(3) In the conditioned medium of fibrosarcoma cell line of HT1080, generated angiostatin was detected by western immuno-blotting. A part of the intra-molecular di-sulfide bond was dissociated in this angiostatin and free-SH was detected. In the angiostatin obtained as an elastase-digested plasminogen fragment, free SH was not detected.
(4) In human colon cancer tissue, larger amounts of low molecular weight fragments of plasminogen were detected compared to normal colon tissue. A part of these plasminogen fragments showed that their intra-molecular disulfide bonds were dissociated.
These results suggest that certain amounts of angiostatin are generated in tumor tissue and may play roles in tumor growth and in metastasis. Since the mechanism to generate angiostatin in tumor tissue seems to be different from elastase digestion of plasminogen, further studies are required to elucidate the mechanism. The possible function and the importance of angiostatin in tumor expansion should be also analyzed.
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