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

Br J Haematol. 1994 Jun;87(2):325-31. doi: 10.1111/j.1365-2141.1994.tb04917.x.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Platelet Aggregation / physiology*
  • Platelet Aggregation Inhibitors / pharmacology
  • Tumor Cells, Cultured

Substances

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