The role of platelets in the pathology of cancer.

Beyond their role in haemostasis, platelets are extremely important in the pathology of cancer. They are implicated in the promotion of growth and angiogenesis in the primary tumour, maintaining the integrity of tumour associated vasculature, and facilitating metastasis. In this thesis, novel mechanisms by which platelet function can influence malignancy and how in turn, malignancy can influence platelet function are demonstrated. Firstly, platelet adhesion and degranulation were shown to induce proliferative, anti-apoptotic, and proangiogenic signalling in ovarian cancer cells that could influence the metastatic potential of ovarian cancer cells in vivo. Secondly, platelets were shown to be capable of protecting cancer cells from shear stress induced damage. This could promote their survival within the circulation during bloodborne metastasis. Thirdly, patients with metastatic cancer were shown to display global platelet hyperreactivity, a phenomenon that could contribute to the high incidence of cancer associated thrombosis.