Gangliosides promote platelet adhesion and facilitate neuroblastoma cell adhesion under dynamic conditions simulating blood flow.
BACKGROUND
Aberrant gangliosides are produced and shed by some tumors into the extracellular milieu. Their concentration is related to disease progression in children with neuroblastoma and in experimental models. The mechanism for this tumor promoting effect is not known.


OBJECTIVE
Here, we investigated the effect of gangliosides on platelet and tumor cell adhesion under shear forces simulating venous and arterial flow.


RESULTS
High shear force increased platelet adhesion 2.5-fold compared to low force. Pre-incubation of platelets with gangliosides increased adhesion at low shear to a level comparable to high shear alone. The addition of gangliosides to platelets perfused at high shear did not further increase adhesion. LAN1 neuroblastoma cells are adherent to collagen in static assays. No effect of either shear or gangliosides was observed on cell adhesion under dynamic conditions. However, when perfused in the presence of platelets, an increase in binding of tumor cells was observed at both shear forces compared to cells alone.


CONCLUSIONS
These results demonstrate that shear and gangliosides increase dynamic platelet adhesion to collagen. In addition, platelets facilitate tumor cell binding. Therefore, by acting as a mediator of platelet activation, gangliosides may promote blood borne metastasis by increasing platelet binding to the vessel wall and in turn facilitate tumor cell arrest in circulation.
Jabbar
Adnan A
AA
Department of Pediatrics, Rush University Medical Center and Rush University, Chicago, Illinois 60612, USA.
Kazarian
Tamara
T
Hakobyan
Narine
N
Valentino
Leonard A
LA
D001783:Blood Flow Velocity; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000378:metabolism*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D013314:Stress, Mechanical
D005732:Gangliosides; D003094:Collagen