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Circulating tumor gangliosides enhance platelet activation
LA Valentino and S Ladisch
Thomas Hazen Thorne Bone Marrow Transplant Center, Rush-Presbyterian-St
Luke's Medical Center, Chicago, IL 60612.
Gangliosides enhance tumor formation in experimental animals, and high
circulating concentrations of gangliosides shed by tumor cells are
associated with rapid progression of human neuroblastoma. We studied these
shed molecules for effects on platelet function, because platelet
activation may play a role in the metastatic process. Preincubation of
normal platelets in patient (tumor ganglioside-containing) serum resulted
in their aggregation upon exposure to a subthreshold concentration (1
microgram/mL) of collagen (up to 34% v < 10% in normal serum) and ATP
release (up to 1.1 nmol/2.5 x 10(7) platelets v < 0.2 in normal serum).
Because circulating shed tumor gangliosides are lipoprotein-associated, we
next assessed the effects of the serum lipoprotein fraction on platelet ATP
release. The patient serum lipoprotein fraction (d > 1.210) enhanced ATP
release (up to 3.1 nmol ATP), whereas the same fraction of normal serum,
and both patient and control lipoprotein-depleted serum fractions (d >
1.210), were inactive (< 0.2 nmol ATP released). Finally, as little as
0.5 mumol/L patient serum gangliosides (purified from the lipoprotein
fraction) caused significantly greater ATP release than did normal serum
gangliosides (P < .01) and caused maximal release at 50 mumol/L (up to
3.0 nmol ATP released v < or = 0.3 nmol released by platelets exposed to
normal serum gangliosides). Purified total human neuroblastoma tumor
gangliosides, detected in the patient serum and isolated from LA-N5 cells,
were highly active; preincubation of platelets with only 5 mumol/L of these
gangliosides resulted in release of 2.5 +/- 0.1 nmol ATP. Thus,
neuroblastoma patient serum, the lipoprotein fraction, and, specifically,
the serum gangliosides enhance platelet activation. This activity appears
to reside particularly in the tumor cell gangliosides, which are shed in
vivo.
Volume 83,
Issue 10,
pp. 2872-2877,
05/15/1994
Copyright © 1994 by The American Society of Hematology
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