Inhibition of collagenolytic activity and metastasis of tumor cells by a recombinant human tissue inhibitor of metalloproteinases

Ofelia A Alvarez, David F. Carmichael, Yves A. DeClerck

Research output: Contribution to journalArticle

229 Citations (Scopus)

Abstract

Metalloproteinases secreted by tumor cells play an important role in metastasis. In the present study, we determined whether an inhibitor of these proteinases could inhibit the ability of tumor cells to degrade collagen and to metastasize. Metalloproteinases with degradative activities for type I collagen, type IV collagen, gelatin, and casein were secreted by a highly metastatic rat embryo cell line (4R) transfected by c-Ha-ras1 (also known as HRAS1). These metalloproteinases were identified by sodium dodecyl sulfate substrate-polyacrylamide gel electrophoresis as 92-kilodalton and 68-kilodalton gelatinolytic enzymes and 48-kilodalton and 45-kilodalton caseinolytic proteinases. A recombinant human tissue inhibitor of metalloproteinases (rTIMP) completely inhibited the proteolytic activities of these enzymes and was also a potent inhibitor of the proteolytic degradation of collagen by intact c-Ha-ras1-transfected cells. The ability of these cells to colonize the lungs after intravenous injection into nude mice was inhibited by 83% when rTIMP was repeatedly injected intraperitoneally into the animals. These data demonstrate that rTIMP is a potent inhibitor of the metalloproteinase activities of these cells and can also inhibit their metastatic potential.

Original languageEnglish
Pages (from-to)589-595
Number of pages7
JournalJournal of the National Cancer Institute
Volume82
Issue number7
StatePublished - Apr 4 1990
Externally publishedYes

Fingerprint

Tissue Inhibitor of Metalloproteinases
Metastasis
Inhibitor
Metalloproteases
Tumors
Tumor
Collagen
Cells
Tissue
Neoplasm Metastasis
Cell
Peptide Hydrolases
Neoplasms
Enzymes
Collagen Type IV
Gelatin
Caseins
Nude Mice
Intravenous Injections
Sodium Dodecyl Sulfate

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging

Cite this

Inhibition of collagenolytic activity and metastasis of tumor cells by a recombinant human tissue inhibitor of metalloproteinases. / Alvarez, Ofelia A; Carmichael, David F.; DeClerck, Yves A.

In: Journal of the National Cancer Institute, Vol. 82, No. 7, 04.04.1990, p. 589-595.

Research output: Contribution to journalArticle

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