Inhibition of vitronectin-mediated haptotaxis and haptoinvasion of MG-63 cells by domain 5 (D5(H)) of human high-molecular-weight kininogen and identification of a minimal amino acid sequence

F Kamiyama; T Maeda; T Yamane; Y H Li; O Ogukubo; T Otsuka; H Ueyama; S Takahashi; I Ohkubo; N Matsui

doi:10.1006/bbrc.2001.5864

Inhibition of vitronectin-mediated haptotaxis and haptoinvasion of MG-63 cells by domain 5 (D5(H)) of human high-molecular-weight kininogen and identification of a minimal amino acid sequence

Biochem Biophys Res Commun. 2001 Nov 9;288(4):975-80. doi: 10.1006/bbrc.2001.5864.

Authors

F Kamiyama¹, T Maeda, T Yamane, Y H Li, O Ogukubo, T Otsuka, H Ueyama, S Takahashi, I Ohkubo, N Matsui

Affiliation

¹ Department of Orthopedics, Nagoya City University Medical School, Mizuho-ku, Nagoya, 467-8601, Japan.

PMID: 11689005
DOI: 10.1006/bbrc.2001.5864

Abstract

We found that human kinin-free high-molecular-weight kininogen (kf-HK) significantly inhibited vitronectin-mediated migration (haptotaxis) and invasive potentiation (haptoinvasion) of osteosarcoma (MG-63) cells but that HK, LK, the common heavy chain of HK and LK, and the light chain (D6(H)) of HK had no inhibitory effect. Recombinant GST-D5(H) (histidine-rich region of HK) obtained from Escherichia coli. (BL21) also inhibited both haptotaxis and haptoinvasion to about 30% of the control level in a dose-dependent manner. These findings suggest that a specific region of D5(H) is responsible for the inhibition of cell haptotaxis and haptoinvasion. Among the seven synthetic peptides covering D5(H), peptide H(479)KHGHGHGKHKNKGK(493) (P-5) inhibited both haptotaxis and haptoinvasion in a dose-dependent manner, suggesting that P-5 could possibly be utilized to prevent primary and secondary metastases of tumor cells.

MeSH terms

Amino Acid Sequence
Cell Movement / drug effects*
Collagen
Dose-Response Relationship, Drug
Drug Combinations
Humans
Kininogens / chemistry*
Kininogens / pharmacology*
Kininogens / therapeutic use
Laminin
Molecular Sequence Data
Molecular Weight
Neoplasm Invasiveness / pathology*
Neoplasm Metastasis / drug therapy
Neoplasm Metastasis / pathology*
Osteosarcoma / drug therapy
Osteosarcoma / pathology*
Peptide Fragments / chemical synthesis
Peptide Fragments / chemistry
Peptide Fragments / pharmacology
Peptide Fragments / therapeutic use
Protein Structure, Tertiary
Proteoglycans
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / pharmacology
Recombinant Fusion Proteins / therapeutic use
Tumor Cells, Cultured
Vitronectin / antagonists & inhibitors*
Vitronectin / pharmacology

Substances

Drug Combinations
Kininogens
Laminin
Peptide Fragments
Proteoglycans
Recombinant Fusion Proteins
Vitronectin
matrigel
Collagen