Characterization of platelet aggregation induced by human colon adenocarcinoma cells and its inhibition by snake venom peptides, trigramin and rhodostomin.

Abstract

SW-480 cells, derived from a primary human colon adenocarcinoma, caused dose-dependent platelet aggregation in heparinized human platelet-rich plasma. SW-480 tumour cell-induced platelet aggregation (TCIPA) was completely inhibited by hirudin (5 U/ml) but unaffected by apyrase (10 U/ml). This TCIPA was also unaffected by cysteine proteinase inhibition with E-64 (10 microM) but was limited by cell pretreatment with phospholipase A2. SW-480 cell suspension caused marked dose-dependent decreases in plasma recalcification times using normal, factor VIII-deficient and factor IX-deficient human plasma. This effect was potentiated with cell lysates but inhibited in intact cells pretreated with sphingosine. SW-480 cell suspension did not affect the recalcification time of factor VII-deficient plasma. Moreover, monoclonal antibody against human tissue factor completely abolished SW-480 TCIPA. Taken together, these data suggest that SW-480 TCIPA arises from SW-480 tissue factor activity expression. Trigramin and rhodostomin, RGD-containing snake venom peptides, which antagonize the binding of fibrinogen to platelet membrane glycogen IIb/IIIa, prevented SW-480 TCIPA. Likewise, synthetic peptide GRGDS as well as monoclonal antibodies against platelet membrane glycoprotein IIb/IIIa and Ib prevent SW-480 TCIPA, which was unaffected by control peptide GRGES. On a molar basis, trigramin (IC50 0.09 microM) and rhodostomin (IC50 0.03 microM) were about 6000 and 18,000 times, respectively, more potent than GRGDS (IC50 0.56 mM).

• Authors: H S Chiang, M W Swaim, T F Huang
• Journal: British journal of haematology (Br J Haematol) Vol. 87 Issue 2 Pg. 325-31 (Jun 1994) ISSN: 0007-1048 [Print] England
• PMID: 7947275 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cysteine Proteinase Inhibitors
• Hirudins
• Intercellular Signaling Peptides and Proteins
• Peptides
• Platelet Aggregation Inhibitors
• trigramin
• rhodostomin
• Fibrinogen
• Phospholipases A
• Phospholipases A2
• Apyrase
• Calcium

Topics

• Adenocarcinoma (pathology)
• Apyrase (pharmacology)
• Calcium (blood)
• Colonic Neoplasms (pathology)
• Cysteine Proteinase Inhibitors (pharmacology)
• Fibrinogen (antagonists & inhibitors)
• Hirudins (pharmacology)
• Humans
• Intercellular Signaling Peptides and Proteins
• Kinetics
• Peptides (pharmacology)
• Phospholipases A (pharmacology)
• Phospholipases A2
• Platelet Aggregation (drug effects, physiology)
• Platelet Aggregation Inhibitors (pharmacology)
• Tumor Cells, Cultured