Inhibition of tumor cell invasion through matrigel by a peptide derived from the domain II region in urinary trypsin inhibition.

Abstract

Urinary trypsin inhibitor (UTI) has a multipotent inhibitory effect on proteases such as trypsin, chymotrypsin, plasmin, human leukocyte elastase, or hyaluronidase. UTI can bind easily to its receptors on various types of tumor cells (human ovarian cancer HOC-I cells, human choriocarcinoma SMT-cc1 cells, and murine Lewis lung carcinoma 3LL cells). Our results show that the UTI receptors of some tumor cells have a possible role in modulating plasmin activity on the cell surface and prevention of tumor cell invasion and metastasis (H. Kobayashi et al., J. Biol. Chem., 269; 20642-20647, 1994). UTI interacts with tumor cells as a negative modulator of the invasive cells. We investigated whether this effect may be mediated by UTI binding to the cell surface receptors. In addition, the role of peptide sequences from each UTI domain and their interaction with tumor cells were investigated. UTI derivatized with biotin or FITC was taken up by tumor cells in a dose-dependent manner. This cell association was inhibited with a monoclonal antibody D1, which specifically recognizes NH2 terminus (domain I) of UTI. The binding was inhibited by fluid phase UTI, but not HI-8, COOH terminus (domain II) of UTI, suggesting that UTI binds to cells through a site in the UTI domain I. Furthermore, we found that UTI, HI-8 and a number of peptides containing Arg-Gly-Pro-Cys-Arg-Ala-Phe-Ile promoted the inhibition of tumor cell invasion. This site corresponds to the plasmin-inhibiting domain within HI-8. The possibility that UTI binding to tumor cells might be involved in the prevention of tumor cell invasion in vitro was excluded since HI-8, lacking domain I, promotes the inhibition of tumor cell invasion with essentially the same affinity as UTI. All these data allow us to conclude that inhibition of tumor cell invasion is mediated by domain II, which possesses anti-plasmin activity.

• Authors: H Kobayashi, J Gotoh, N Kanayama, Y Hirashima, T Terao, D Sugino
• Journal: Cancer research (Cancer Res) Vol. 55 Issue 9 Pg. 1847-52 (May 01 1995) ISSN: 0008-5472 [Print] United States
• PMID: 7728751 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Drug Combinations
• Glycoproteins
• Laminin
• Peptide Fragments
• Proteoglycans
• Receptors, Cell Surface
• Trypsin Inhibitors
• urinary trypsin inhibitor receptor
• matrigel
• Collagen
• urinastatin

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Monoclonal (metabolism)
• Antibody Specificity
• Antineoplastic Agents
• Choriocarcinoma (drug therapy, metabolism, pathology)
• Collagen
• Drug Combinations
• Glycoproteins (metabolism, pharmacology)
• Humans
• Laminin
• Leukemia, Promyelocytic, Acute (drug therapy, metabolism, pathology)
• Mice
• Molecular Sequence Data
• Neoplasm Invasiveness
• Peptide Fragments (metabolism, pharmacology)
• Proteoglycans
• Rabbits
• Receptors, Cell Surface (metabolism)
• Trypsin Inhibitors (metabolism, pharmacology)