The carboxyl-terminal half region of ADAMTS-1 suppresses both tumorigenicity and experimental tumor metastatic potential

Biochem Biophys Res Commun. 2004 Jul 9;319(4):1327-33. doi: 10.1016/j.bbrc.2004.05.105.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins
  • ADAMTS1 Protein
  • Amino Acid Motifs
  • Animals
  • CHO Cells
  • Cricetinae
  • Disintegrins / chemistry
  • Disintegrins / genetics
  • Disintegrins / metabolism*
  • Lung / cytology
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Metalloendopeptidases / chemistry
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Metastasis*
  • Neoplasm Transplantation
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism*
  • Neoplasms, Experimental / pathology
  • Neovascularization, Pathologic

Substances

  • Disintegrins
  • ADAM Proteins
  • ADAMTS1 Protein
  • Adamts1 protein, mouse
  • Metalloendopeptidases