The carboxyl-terminal half region of ADAMTS-1 suppresses both tumorigenicity and experimental tumor metastatic potential.
ADAMTS-1 is an ECM-anchored metalloproteinase with proteoglycan-degrading activity as well as an angiogenesis inhibiting activity. Here, we examined the effects of ADAMTS-1 overexpression on in vivo tumor growth and tumor metastasis. Overexpression of only the C-terminal half region of ADAMTS-1, consisting of TSP type I motifs and the spacer region, suppressed Chinese hamster ovary (CHO) tumor growth in mice. In addition, a significant reduction in tumor metastatic potential was observed in ADAMTS-1-transfected CHO cells in an experimental metastasis assay. Furthermore, deletional analyses revealed that the C-terminal half region of ADAMTS-1 is responsible for its experimental metastasis-inhibitory activity. Our data suggest that the C-terminal half region of ADAMTS-1 has therapeutic potential as an inhibitor of tumor growth and metastasis.
Kuno
Kouji
K
Center for the Development of Molecular Target Drugs, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan. kkuno@kenroku.kanazawa-u.ac.jp
Bannai
Kenji
K
Hakozaki
Michinori
M
Matsushima
Kouji
K
Hirose
Kunitaka
K
D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D020816:Amino Acid Motifs; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D019483:Disintegrins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic
D019483:Disintegrins; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C486323:Adamts1 protein, mouse; D008666:Metalloendopeptidases