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The role of blood platelets in the processes of haematogenous metastasis

Skinner, Vernon Oliver; (1995) The role of blood platelets in the processes of haematogenous metastasis. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Tumour cells have been shown to interact with platelets and thereby facilitate metastatic spread of cancer via the blood. In this study, the interaction of human liver tumour cell lines with platelets was investigated. All cell lines caused platelet aggregation in the presence of Ca2+. Platelet aggregation was of two types. The first type was ADP mediated, occurring in the absence of blood plasma, and was inhibited by aspirin ('plasma-independent'). The second, required low concentrations of plasma. It involved activation of coagulation, resulting in generation of thrombin ('plasma- dependent'). Platelet aggregation was accompanied by platelet degranulation as determined by ATP (dense granule marker) and N-acetyl-β-D- glucuronidase (lysosomal marker) measurements. Plasma-dependent proaggregatory activity was released from four of the five hepatoma cell lines, and was manifested only in viable cells. In the non-metastatic cell line, HepG2, the activity remained bound to the outer surface of the cell, and was present even in non- viable cells. Full integrity of the blood coagulation cascade was essential for platelet aggregating activity of the hepatoma cells. In particular, Factor X, and additionally with Mahlavu cells. Factor VII, was necessary for platelet aggregating activity. Procoagulatory activity of all the cell lines was mediated partially by Factor VII. In addition, HepG2 released a Factor VII-dependent coagulation inhibitor. Endothelial cells form a natural barrier to metastatic spread. The inhibitory effects of cultured endothelial cells on the activity of hepatoma cells were therefore studied. Endothelial cells were found to inhibit Mahlavu- and HepG2-induced platelet aggregation, but not that induced by SK55 cells. This effect was due mainly to prostacyclin (PGI2). Nitric oxide was found to mask hepatoma-associated platelet aggregating activity of HepG2 cells, but not that of Mahlavu or SK55 cells. It was concluded that while both metastatic and non-metastatic hepatoma cell lines can activate platelets, differences in their characteristics may go some way in explaining the basis of metastatic behaviour.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The role of blood platelets in the processes of haematogenous metastasis
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10098991
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