The Arg-Gly-Asp-containing peptide, rhodostomin, inhibits in vitro cell adhesion to extracellular matrices and platelet aggregation caused by saos-2 human osteosarcoma cells.
Saos-2 cells, derived from a primary human osteosarcoma, caused dose-dependent platelet aggregation in heparinised human platelet-rich plasma. Saos-2 tumour cell-induced platelet aggregation (TCIPA) was completely inhibited by hirudin but unaffected by apyrase. The cell suspension shortened the plasma recalcification times of normal, factor VIII-deficient and factor IX-deficient human plasmas in a dose-dependent manner. However, the cell suspension did not affect the recalcification time of factor VII-deficient plasma. Moreover, a monoclonal antibody (MAb) against human tissue factor completely abolished TCIPA. Flow cytometric analysis using anti-integrin MAbs as the primary binding ligands demonstrated that the integrin receptors alpha v beta 3, alpha 5 beta 1 and alpha 6 beta 1 were present of Saos-2 cells, which might mediate tumour cell adhesion to extracellular matrix. Rhodostomin, an Arg-Gly-Asp (RGD)-containing snake venom peptide which antagonises the binding of fibrinogen to platelet membrane glycoprotein IIb/IIIa, prevented Saos-2 TCIPA as well as tumour cell adhesion to vitronectin, fibronectin and collagen type I. Likewise, the synthetic peptide Gly-Arg-Gly-Asp-Ser (GRGDS) showed a similar effect. On a molar basis, rhodostomin was about 18,000 and 1000 times, respectively, more potent than GRGDS in inhibiting TCIPA and tumour cell adhesion.
Chiang
H S
HS
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Yang
R S
RS
Huang
T F
TF
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001081:Apyrase / Q000494:pharmacology; D001778:Blood Coagulation Disorders / Q000097:blood; D001779:Blood Coagulation Factors / Q000502:physiology; D001859:Bone Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D012516:Osteosarcoma / Q000473:pathology*; D010455:Peptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology; D011485:Protein Binding / Q000187:drug effects; D013917:Thrombin / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology
D000911:Antibodies, Monoclonal; D001779:Blood Coagulation Factors; D006629:Hirudins; D016023:Integrins; D009363:Neoplasm Proteins; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; C072026:rhodostomin; C047981:arginyl-glycyl-aspartic acid; C049554:glycyl-arginyl-glycyl-aspartyl-serine; D013917:Thrombin; D001081:Apyrase