2000 Fiscal Year Final Research Report Summary
The experimental study of specific COX-2 inhibitors applied to non-surgical therapy of postoperative recurrences and distant metastasis of lung cancer.
| Project/Area Number |
11670160
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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 |
Pathological medical chemistry
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
KOZAKI Ken-ichi Aichi Cancer Center, Section Head, 分子腫瘍学部, 主任研究員 (50270715)
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| Project Period (FY) |
1999 – 2000
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| Keywords | cyclooxygenase2 / tumor invasion and metastasis / postoperative recurrences / high metastatic human lung cancer cell line / specific cyclooxygenase 2 inhibitors |
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| Research Abstract |
Although a large number of studies have been conducted, yielding considerable information about the metastatic processes, very little is known about how cancer cells propagate distantmetastasis and about target molecules applied to non-surgical therapy of postoperative recurrences and distant metastasis. Identification of molecules with a crucial role in the distant spread of lungcancer cells has been hampered by scarcity of an appropriate experimental model system. We recently reported the successful establishment of a highly metastatic human lung cancer cell line, NCI-H460-LNM35 (hereafter referred to as LNM35), which is capable of spontaneous metastases not only via hematogenous but also lymphogenous routes with a 100% incidence. In the present study, we found that cyclooxygenase 2 (COX-2) expression llevels correlated well with the capabilities of LNM35 for not only in vitro motility and invasion but also in vivo metastasis, while specific COX-2 inhibitors were shown for the first time to reduce lung cancer metastasis in vivo. The present study thus strengthens our previously stated concept that COX-2 may play a role in the metastatic processes of lung cancers and suggests the potentially clinical usefulness of specific COX-2 inhibitors for the treatment of lung cancer cases. Further, expression-profiling analysisrevealed that, while COX-2 itself is known to be inducible in inflammation, up-regulation of various proinflammatory cytokines and angiogenic chemotactic chemokines was present in LNM35. This suggest that lung cancer cells may mimic inflammatory cells in the process of metastasis.
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