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ツゲ ヒデアキ
TSUGE HIDEAKI
津下 英明 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2002/01 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Structure-based design of specific cathepsin inhibitors and their application to protection of bone metastases of cancer cells |
| 執筆形態 | その他 |
| 掲載誌名 | ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS |
| 出版社・発行元 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 巻・号・頁 | 397(2),pp.305-311 |
| 著者・共著者 | N Katunuma,H Tsuge,M Nukatsuka,T Asao,M Fukushima |
| 概要 | We report the antihypercalcemic and antimeta-static effects of CLIK-148 in vivo, which is a specific inhibitor of cathepsin L. The decalcification during bone absorption is followed by the degradation of type-1 collagen by osteoclastic cathepsins. Tumor-bearing osteoclasts or TNF-alpha-activated osteoclasts secrete large amounts of cysteine proteases, especially procathepsin L, which powerfully degrade type-1 collagen leading to tumor-associated bone absorption and release of bone calcium. The bone pit formations in vitro, which are caused by osteoclasts derived from human bone marrow cells activated by RANKL and M-CSF and also by mice osteoclasts activated by TNF-alpha, are significantly prevented by CLIK-148 treatment. We evaluated the in vivo inhibitory effect of malignant hypercalcemia induced by LJC-1 human mandibular cancer inoculation by CLIK-148 treatment, and the CLIK-148 treatment significantly protected against the tumor-induced hypercalcemia. On the protection of bone metastasis of colon 26 PMF-15 implanted to mouse calvaria, CLIK-148 treatment significantly inhibited calvaria bone absorption (direct metastasis). The CLIK-148 treatment also reduced distant bone metastasis to the femur and tibia of melanoma A375 tumors implanted into the left ventricle of the heart. (C) 2002 Elsevier Science. |
| DOI | 10.1006/abbi.2001.2709 |
| ISSN | 0003-9861 |