Tumour angiogenesis: pathophysiology and clinical significance

In the 1970s it was first proposed that tumours depended on the establishment of a microcirculation in order to grow beyond a few millimetres. Thereafter, the search to prove this hypothesis increased strongly and by the end of the 1980s, evidence was given that tumours were angiogenesis-dependent and metastatic cells were only shed after the tumour had established its microcirculation. The process of neovascularization is regulated by numerous growth factors, vascular endothelial cells, and matrix proteins released from host stromal cells such as macrophages and mast cells. The process of tumour growth and metastasis involves tumour cell-host cell and cell-matrix interactions and many of the underlying mechanisms of these interactions still remain to be elucidated. Although in a minority of cases treatment of solid tumours has been effectively improved, for the majority of cases more adequate treatment is still required to reduce the mortality rate. It has been proposed only recently that specific targeting of the angiogenic process might inhibit tumour growth and metastasis. This promising field of research is now exponentially growing. It is the purpose of this review to summarize current knowledge on the pathophysiology and clinical significance of tumour angiogenesis.