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

We found that human kinin-free high-molecular-weight kininogen (kf-HK) sign ificantly inhibited vitronectin-mediated migration (haptotaxis) and invasiv e potentiation (haptoinvasion) of osteosarcoma (MG-63) cells but that HH, L K, the common heavy chain of RK and LK, and the light chain (D6(H)) of HK h ad no inhibitory effect. Recombinant GST-D5(H) (histidine-rich region of RK ) 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 synth etic peptides covering D5(H), peptide H(479)KHGHGHGKHKNKGK(493) (P-5) inhib ited both haptotaxis and haptoinvasion in a dose-dependent manner, suggesti ng that P-5 could possibly be utilized to prevent primary and secondary met astases of tumor cells. (C) 2001 Academic Press.