Platelets mediate tumor cell adhesion to the subendothelium under flow conditions: involvement of platelet GPIIb-IIIa and tumor cell alpha(v) integrins.
The aim of our study was to explore the role of platelets and their specific integrin receptors in mediating the interaction of 4 human tumor cell lines (3 melanoma and 1 carcinoma) with the extracellular matrix (ECM) under static and arterial flow conditions. Under static conditions, all 4 cell lines adhered to the ECM. The adhesion capacity of all 4 cell lines was virtually abolished by application of flow during incubation with the ECM. Under static conditions, tumor cell adhesion was not affected by adding platelets to the cell suspension and was slightly reduced by pre-coating the ECM with platelets prior to the addition of tumor cells. In contrast, under flow conditions, platelets significantly increased tumor cell adhesion to the ECM, the enhancing effect being more pronounced when platelets were pre-incubated with the ECM prior to the addition of tumor cells than when incubated simultaneously with the cells. Platelet-mediated tumor cell adhesion under flow was markedly inhibited by blockade of the platelet GPIIb-IIIa or of the tumor cell alpha(v) integrins. Platelets of a Glanzmann thrombastenia (GT) patient were unable to support tumor cell adhesion to the ECM under flow. Our results suggest that the interaction of tumor cells with subendothelium-bound platelets under flow conditions is mediated by platelet GPIIb-IIIa and by tumor cell alpha(v) integrins independently of the nature of the beta subunit.
Dardik
R
R
National Hemophilia Center and Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel.
Kaufmann
Y
Y
Savion
N
N
Rosenberg
N
N
Shenkman
B
B
Varon
D
D
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology*; D002448:Cell Adhesion; D004730:Endothelium, Vascular; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D018056:Hemorheology; D006801:Humans; D039564:Integrin alphaV; D008545:Melanoma / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology*; D011817:Rabbits; D019030:Receptors, Vitronectin / Q000502:physiology; D013915:Thrombasthenia / Q000473:pathology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D016326:Extracellular Matrix Proteins; D039564:Integrin alphaV; D009363:Neoplasm Proteins; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; C046617:arginyl-glycyl-aspartyl-serine