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, con...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2004-07, Vol.319 (4), p.1327-1333
Main Authors: Kuno, Kouji, Bannai, Kenji, Hakozaki, Michinori, Matsushima, Kouji, Hirose, Kunitaka
Format: Article
Language:English
Subjects:
ADAM
ADAM Proteins
ADAMTS1 Protein
Amino Acid Motifs
Animals
CHO Cells
Cricetinae
Disintegrins - chemistry
Disintegrins - genetics
Disintegrins - metabolism
Extracellular matrix
Lung - cytology
Lung - metabolism
Lung - pathology
Male
Metalloendopeptidases - chemistry
Metalloendopeptidases - genetics
Metalloendopeptidases - metabolism
Metalloproteinase
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Metastasis
Neoplasm Transplantation
Neoplasms, Experimental - genetics
Neoplasms, Experimental - metabolism
Neoplasms, Experimental - pathology
Neovascularization, Pathologic
Tumor growth
Tumor metastasis
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2004.05.105