Effects of divalent cations on the interaction of platelets with tumor cells: aggregation and perfusion studies with two homologous human systems.
The effects of chelation of divalent cations in the interaction of platelets and tumor cells has been studied in a homologous human system using human platelet-rich plasma and two tumor cell lines of human origin: SKNMC (neuroblastoma) cells, which cause platelet aggregation by an adenosine diphosphate-dependent mechanism, and U87MG (glioblastoma) cells, which function by a thrombin-dependent mechanism. When added at zero time, citrate 14 mmol/L completely abolished aggregation in heparinized (5 U/ml) platelet-rich plasma by either cell line, but the degree of inhibition was reduced by later addition of the chelating agent. Calcium citrate 8 mmol/L reduced by only 10%, indicating that citrate anion was not responsible for the inhibition. Addition of Ca++ or Mg++ alone or in combination at concentrations up to 1.5 mmol/L did not reverse the inhibition. Addition of higher concentrations of Ca++ (2 mmol/L) caused immediate clotting, whereas concentrations of Mg++ up to 6 mmol/L were without effect. Inhibition could be reversed by washing the platelets free of citrate and resuspending in heparinized platelet-rich plasma. Aggregation by either cell line was inhibited by EDTA and EGTA. In the Baumgartner perfusion apparatus, platelet interaction with subendothelium was increased about 50-fold in the presence of SKNMC cells, but this effect was also abolished after addition of citrate. After addition of U87MG cells to heparinized PRP, there was a 400-fold increase in platelet interaction with subendothelium, and complex thrombi containing red cells, white cells, and fibrin were formed. This stimulation was reduced to control levels by addition of citrate.(ABSTRACT TRUNCATED AT 250 WORDS)
D001792:Blood Platelets / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D005910:Glioma / Q000097:blood*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008274:Magnesium / Q000494:pharmacology*; D009447:Neuroblastoma / Q000097:blood*; D010477:Perfusion; D010974:Platelet Aggregation / Q000187:drug effects*
D002951:Citrates; D019343:Citric Acid; D006493:Heparin; D008274:Magnesium; D002118:Calcium