Characterization of platelet aggregation induced by human breast carcinoma and its inhibition by snake venom peptides, trigramin and rhodostomin.

Abstract

MCF-7 cells, a metastatic human breast carcinoma line, caused dose-dependent platelet aggregation in heparinized human platelet-rich plasma (PRP). MCF-7 tumor cell-induced platelet aggregation (TCIPA) was almost blocked by apyrase (0.5 U/ml) and completely inhibited by hirudin (5 U/ml). This TCIPA was unaffected by cysteine proteinase inhibition with E-64 (10 microM), but was limited by cell pretreatment with phospholipase A2. MCF-7 cell suspension caused marked, dose-dependent decrease in plasma recalcification times using normal, Factor VIII-deficient, and Factor IX-deficient human plasma. This effect was potentiated in cell lysates but was inhibited in intact cells preincubated with sphingosine. MCF-7 cell suspension did not affect the recalcification time of Factor VII-deficient plasma. Taken together, these data suggest that MCF-7 TCIPA arises from MCF-7 tissue factor activity expression. Trigramim and rhodostomin, RGD-containing snake venom peptides which antagonized the binding of fibrinogen to platelet membrane glycoprotein IIb/IIIa, prevented MCF-7 TCIPA. Likewise, synthetic peptide GRGDS as well as monoclonal antibodies against human tissue factor, platelet membrane glycoprotein IIb/IIIa and Ib prevented MCF-7 TCIPA, which was unaffected by control peptide GRGES. On a molar basis, trigramin (IC50, 0.1 microM) and rhodostomin (IC50, 0.03 microM), were about 5,000 and 18,000 times, respectively, more potent than GRGDS (IC50, 0.54 mM).

• Authors: H S Chiang, M W Swaim, T F Huang
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 33 Issue 3 Pg. 225-35 (Mar 1995) ISSN: 0167-6806 [Print] Netherlands
• PMID: 7749150 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Crotalid Venoms
• Cysteine Proteinase Inhibitors
• Hirudins
• Intercellular Signaling Peptides and Proteins
• Oligopeptides
• Peptides
• Platelet Aggregation Inhibitors
• glycyl-arginyl-glycyl-glutamyl-serine
• trigramin
• rhodostomin
• glycyl-arginyl-glycyl-aspartyl-serine
• Phospholipases A
• Phospholipases A2
• Apyrase
• Sphingosine

Topics

• Adenocarcinoma (blood, drug therapy)
• Animals
• Antibodies, Monoclonal (pharmacology)
• Apyrase (pharmacology)
• Breast Neoplasms (blood, drug therapy)
• Crotalid Venoms (pharmacology)
• Cysteine Proteinase Inhibitors (pharmacology)
• Female
• Hirudins (pharmacology)
• Humans
• Intercellular Signaling Peptides and Proteins
• Oligopeptides (pharmacology)
• Peptides (pharmacology)
• Phospholipases A (pharmacology)
• Phospholipases A2
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (pharmacology)
• Sphingosine (pharmacology)
• Tumor Cells, Cultured