Interactions between cancer cells and the endothelium in metastasis

The haematogenous phase of cancer metastasis facilitates the transport of m etastatic cells within the blood and incorporates a sequence of interaction s between circulating intravascular cancer cells and the endothelium of blo od vessels at the sites of tumour cell arrest. Initial interactions involve mechanical contact and transient adhesion, mediated by endothelial selecti ns and their ligands on the neoplastic cells. This contact initiates a sequ ence of activation pathways that involves cytokines, growth factors, bioact ive lipids, and reactive oxygen species produced by either the cancer cell or the endothelium. These molecules elicit expression of integrin adhesion molecules in cancer cells and the endothelium, matrix metalloproteinases, a nd chemotactic factors that promote the attachment of tumour cells to the v essel wall and/or transvascular penetration. Induction of endothelial free radicals can be cytotoxic to cancer cells. Collectively, the sum of these i nteractions constitutes an interdependent relationship, the outcome of whic h determines the fate of the metastatic process, Copyright (C) 2000 John Wi ley & Sons, Ltd.