The use of a perfusion model for studying aggregation and attachment of platelets and tumor cells at subendothelial surfaces.
The Baumgartner perfusion apparatus has been applied to the study of the interaction of platelets and tumor cells and their attachment to subendothelial structures. Cells derived from an anaplastic murine tumor (Hut 20 line) induced platelet aggregation and were included in platelet thrombi that deposited on vascular subendothelium in perfusion experiments with heparinized human blood. In contrast, perfusion of blood samples containing cells from a line derived from a human epithelial carcinoma of the lung (A549 line), which did not interact with platelets, resulted in the deposition of platelets alone, with no tumor cells or blood cells other than platelets being observed in the thrombus. Extremely large platelet-tumor cell thrombi were found at the vascular surface in Hut 20 perfusions using vessel segments which had been treated with alpha-chymotrypsin. These large heterogeneous thrombi perturbed blood flow through the system and entrapped both erythrocytes and white cells. In order to quantitate the deposition of tumor cells, Hut 20 cells were labeled with 125I-deoxyuridine and perfused in whole blood at a concentration of 3.7x10(5)/ml. Tumor cell incorporation into platelet-tumor cell thrombi on chymotrypsinized segments yielded about 30,000 cpm/mg of vascular tissue but this value was reduced some 2 orders of magnitude by the inclusion of PGE1 (1 ng/ml of perfusing blood; 2.8 microM) in parallel samples. Aspirin at 100 microM reduced tumor cell-dependent platelet aggregation but did not decrease the platelet-dependent deposition of radiolabeled Hut 20 cells on vascular subendothelium, suggesting the release reaction may not be of major significance in this interaction. Tumor cell-induced platelet aggregation was not observed in a perfusion experiment using blood from a patient with severe von Willebrand's disease. However addition of 0.1 vol of ABO-compatible, heterologous plasma as a source of factor VIII to the von Willebrand blood sample restored the platelet-dependent deposition of radiolabeled tumor cells to control values.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002448:Cell Adhesion; D002460:Cell Line; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009369:Neoplasms / Q000503:physiopathology*; D009360:Neoplastic Cells, Circulating; D010477:Perfusion; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation