| Project/Area Number |
61480230
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | Juntendo University |
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Principal Investigator |
OGAWA Hideoki Juntendo university School of Medicine, 医学部皮膚科, 教授 (30053151)
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| Co-Investigator(Kenkyū-buntansha) |
YAGUTHI Hitosi Juntendo university School of Medicine, 医学部皮膚科, 助手 (60191095)
TAKAMORI Kenji Juntendo university School of Medicine, 医学部皮膚科, 助教授 (40053144)
中尾 裕史 順天堂大学, 医学部皮膚科, 研究生
TSUBOI Ryoji Juntendo university School of Medicine, 医学部皮膚科, 助手 (70221421)
KURITA Yoriyuki Juntendo university School of Medicine, 医学部皮膚科, 助手 (80201474)
NAKAO Hiroshi Juntendo university School of Medicine
今井 龍介 順天堂大学, 医学部・皮膚科, 助手 (70175214)
内藤 勝一 順天堂大学, 医学部・皮膚科, 助手 (10138307)
白井 まさ子 順天堂大学, 医学部・皮膚科, 助手 (60162757)
木村 太紀 順天堂大学, 医学部・皮膚科, 助手 (00161563)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1986: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | malignant melanoma / fibrosarcoma / cutaneous malignant tumor / fibroblast / protease / protease inhibitor / invasion / 転移 / 増殖 / 悪性黒色腫 / インヒビター |
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| Research Abstract |
Role of various proteases and there inhibitors on the invasion and metastasis of malignant melanoma were investigated.
1. The effect of various protease inhibitors on cultured melanoma cells were studied. Potent thiol protease inhibitors, leupeptin, antipain and intracellular cathepsin B and Hb-hydrolase.
2. The correlation between protease activities and invasive and metastaic potentials was investigated by comparing three different kinds of cuteneous tumors. Extracts from tumor homogenates of squamous cell carcinoma(SCC), basal cell epithelioma(BCE) and seborrhic keratosis(SK) were prepaired to examine the activity of various proteases. Type I collagenase activity of SCC was 9-fold higher than that of SK, and Type IV collagenase was 3-fold SCC was 9-fold higher than that of SK, and Type IV collagenase was 3-fold higher per tissue DNA. Type I and IV collagenase of BCE were elevated per tissue protean. And, correlation was found between the level of cell differention in SCC and the activ
… More
ities of cathepsin B and Type I collagenase poorly differenciated SCC exhibited a tendency to have higher Proteinase activities. proteases that showed high activities in malignant tumor homogenate may be related to the degradation of the surrounding cell matrix.
3. The interaction between fibrosarcoma cell and tumor surrounding cells or matrices was investigated by measuring the various intracellular protease activities. Conditioned medium obtained from fibrosarcoma cell(HT-1080) contained a low molecular weight substance which selectively induced an increase in the cathepsin B and hemoglobin-hydrolase activities of normal human fibroblast. Furthermore, the lysosomal protease activities of fibrosarcoma cells which were cultured with and without stromal materials were measured. Results from these comparisons showed that cathepsin B activity increased in the presence of these stromas. Tumor cells and tumor surrounding normal fibroblast increases the protease activities through the interaction of tumor cell and tumor surrounding fibroblast or matrices, resulting in the degrading of stromal tissues to facilitate the invasion of tumor cells. Less
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