Characterisation of platelet aggregation induced by PC-3 human prostate adenocarcinoma cells and inhibited by venom peptides, trigramin and rhodostomin.

Abstract

PC-3 cells, a metastatic human prostate adenocarcinoma line, caused dose-dependent platelet aggregation in heparinised human platelet-rich plasma (PRP). PC-3 tumour cell-induced platelet aggregation (TCIPA) was completely inhibited by hirudin (5 U/ml) and limited by increasing concentrations of apyrase. This TCIPA was unaffected by cysteine proteinase inhibition with E-64 (10 microM), but was limited by cell pretreatment with phospholipase A2. PC-3 cell suspension caused marked, dose-dependent decreases in plasma recalcification times using normal, Factor VIII-deficient and Factor IX-deficient, but not Factor VII-deficient, human plasma. This effect was potentiated in cell lysates, but was inhibited in intact cells preincubated with sphingosine. Overall, these data suggest that PC-3 TCIPA arises from PC-3 tissue factor activity expression. Trigramin and rhodostomin, RGD-containing snake venom peptides which antagonise the binding of fibrinogen to platelet membrane glycoprotein IIb-IIIa, prevented PC-3 TCIPA. Similarly, synthetic peptide GRGDS as well as monoclonal antibodies against platelet membrane glycoproteins IIb-IIIa and Ib prevented PC-3 TCIPA, which was unaffected by control peptide GRGDS. On a molar basis, trigramin (IC50, 0.11 microM) and rhodostomin (IC50, 0.03 microM) were approximately 5000 and 18000 times, respectively, more potent than GRGDS (IC50, 0.56 mM).

• Authors: M W Swaim, H S Chiang, T F Huang
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 32A Issue 4 Pg. 715-21 (Apr 1996) ISSN: 0959-8049 [Print] England
• PMID: 8695278 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Cysteine Proteinase Inhibitors
• Glycoproteins
• Hirudins
• Intercellular Signaling Peptides and Proteins
• Peptides
• Platelet Aggregation Inhibitors
• trigramin
• rhodostomin
• Fibrinogen
• Phospholipases A
• Phospholipases A2
• Thrombin
• Apyrase

Topics

• Adenocarcinoma (enzymology, pathology)
• Antibodies, Monoclonal (pharmacology)
• Apyrase (pharmacology)
• Cysteine Proteinase Inhibitors (pharmacology)
• Fibrinogen (antagonists & inhibitors)
• Glycoproteins (immunology)
• Hirudins (pharmacology)
• Humans
• Intercellular Signaling Peptides and Proteins
• Male
• Peptides (pharmacology)
• Phospholipases A (antagonists & inhibitors)
• Phospholipases A2
• Platelet Aggregation (drug effects, physiology)
• Platelet Aggregation Inhibitors (pharmacology)
• Prostatic Neoplasms (enzymology, pathology)
• Thrombin (metabolism)
• Tumor Cells, Cultured