A novel Arg-Gly-Asp containing peptide specific for platelet aggregation and its effect on tumor metastasis: a possible mechanism of RGD peptide-mediated inhibition of tumor metastasis.
A novel cyclic tetrapeptide containing L-arginine-glycine-L-aspartic acid-L-phenylglycine (cyclo-RGDPhg) was synthesized and found to be a potent inhibitor of platelet aggregation induced by highly metastatic murine squamous cell carcinoma (SCCVII) cells (IC50 = 3.3 microM) as well as ADP (1.5 microM). This cyclic peptide, however, showed similar or less inhibitory activities on adhesion of SCCVII cells to fibronectin, vitronectin and type IV collagen as compared with those of parent linear tetrapeptide, RGDS. These results show that cyclo-RGDPhg peptide is a highly specific antagonist for gpIIb/IIIa on platelets. Moreover, this peptide failed to suppress pulmonary metastasis of SCCVII cells in an experimental metastasis model. These results indicate that RGD peptide-mediated inhibition of tumor metastasis is attributed to the suppression of cell adhesion but not platelet aggregation. These also suggest that platelet aggregation is not an essential step during blood circulation of tumor cells for the completion of metastasis.
Isoai
A
A
Research Center, Asahi Glass Co. Ltd., Yokohama, Japan.
Ueno
Y
Y
Giga-Hama
Y
Y
Goto
H
H
Kumagai
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D001224:Aspartic Acid / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D002448:Cell Adhesion / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D010456:Peptides, Cyclic; D010974:Platelet Aggregation / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects; D019096:Vitronectin
D016588:Anticarcinogenic Agents; D005353:Fibronectins; D006023:Glycoproteins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019096:Vitronectin; C077078:cyclo-RGDPhg; D001224:Aspartic Acid; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen; D001120:Arginine; D005998:Glycine