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) 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.
Kamiyama
F
F
Department of Orthopedics, Nagoya City University Medical School, Mizuho-ku, Nagoya, 467-8601, Japan.
Maeda
T
T
Yamane
T
T
Li
Y H
YH
Ogukubo
O
O
Otsuka
T
T
Ueyama
H
H
Takahashi
S
S
Ohkubo
I
I
Matsui
N
N
D000595:Amino Acid Sequence; D002465:Cell Movement / Q000187:drug effects*; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D007704:Kininogens / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D007797:Laminin; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology*; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017434:Protein Structure, Tertiary; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D004338:Drug Combinations; D007704:Kininogens; D007797:Laminin; D010446:Peptide Fragments; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D019096:Vitronectin; C059485:matrigel; D003094:Collagen