1995 Fiscal Year Final Research Report Summary
Platelet-mediated killing of tumor cells : effectors and adhesive molecules
| Project/Area Number |
05671936
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory medicine
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| Research Institution | Ehime College of Health Science |
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Principal Investigator |
OKADA Mariko Ehime College of Health Science Dep. of Clin. Lab. Technol. (Associate Professor), 臨床検査学科, 助教授 (60111118)
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| Co-Investigator(Kenkyū-buntansha) |
HITSUMOTO Yasuo Ehime University, school of Med.(Assistant Professor), 医学部・附属病院, 助手 (90136333)
TOMINAGA Akio Ehime College of Health Science Dep. of Clin. Lab. Technol. (Assistant Professor, 臨床検査学科, 助教授 (90036450)
SAGAWA Terutaka Ehime College of Health Science Dep. of Clin. Lad. Technol. (Associate Professor, 臨床検査学科, 助手 (90162320)
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| Project Period (FY) |
1993 – 1995
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| Keywords | platelets / tumor cell killing / cyclooxygenase / thromboxane A2 / nitric oxide / adhesion molecule / N-acetylglucosamine |
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| Research Abstract |
We have tried to identify the cytotoxic effectors in the platelet-mediated tumour cell killing, using two tumour cell lines, K562 (a chronic myelogenic leukemic cell line) and LU99A (alung cancer cell line), which are both sensitive to platelet cytotoxicity. Cyclooxygenase inhibitors, acetylsalicylic acid (ASA) and indomethacin, effectively inhibited the platelet-mediated killing of K562 cells, but not that of LU99A cells. In contrast, inhibitors of the nitric oxide (NO) pathway, NG-nitro-L-arginine (L-NA), haemoglobin and methylene blue, reduced the cytotoxic activity of platelets against LU99A, but not against K562. Synthetic analogues of platelet-cyclooxygenase products thromboxane A2/prostaglandin H2 (TXA2/PGH) exerted cytotoxicity against K562 cells but not against LU99A cells. Electron microscopic study showed that TXA2/PGH2 analogues indiced bleb formation and disruption of plasma membrane of K562 cells. K562 cells enhanced the production of TXA2 by platelets, as inferred from the accumulation of thromboxane B2 (TXB2), a spontaneous hydrolyzed product of TXA2. LU99A cells had no such effects. These results indicate that platelets kill these two tumour cell lines through different mechanisms. In K562, the cyclooxygenase products, TXA2/PGH2, are suggested to play a significant role, but in LU99A, NO pathway is suggested to be involved.
We have also tried to identify the adhesion molecules in this reaction. It is suggested that N-acetylgucosamine is involved but P selectin is not involved in this reaction. Further study must be done in order to know what kind of molecules play roles in the adhesion between platelets and target tumor cells.
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