The importance of blood cell-vessel wall interactions in tumour metastasis.

Tumour cell dissemination is a complex process, depending on the ability of malignant cells to escape from the primary tumour and penetrate and flow through the bloodstream. Circulating tumour cells can adhere to the vessel wall, dissolve the basal lamina and extravasate, giving origin to metastases. Interactions between tumour cells, blood platelets and leukocytes favour tumour cell adhesion to the vessel wall, migration in extravascular spaces and growth in secondary sites. The biochemical and molecular mechanisms regulating tumour cell adhesion to the vessel wall and intercellular contacts have been studied extensively in recent years. Moreover, it has been shown that either tumour cells or blood cells release growth factors and inflammatory proteins, such as cytokines and chemokines, that may be involved in tumour cell migration and proliferation. Finally, tumour cells and cells of the surrounding tissue possess procoagulant and fibrinolytic properties that may be important in modulating the extracellular matrix around the tumour, to allow tumour cell invasion and progression. We have described the cell types (i.e. blood platelets, leukocytes, endothelial cells), the matrix components (i.e. fibronectin, thrombospondin and laminin) and the growth factors/cytokines (i.e. platelet-derived growth factor, transforming growth factor beta, tumour necrosis factor) involved in these processes. In particular, we have described cell-cell and cell-matrix interactions, cell migration and release of growth factors, cytokines, chemotactic peptides and proteolytic enzymes. This survey has also considered a few innovative approaches for the prevention and cure of cancer and metastasis that are based on these new concepts.