Migration of capillary endothelial cells is stimulated by tumour-derived factors

Angiogenesis, the growth of new blood vessels, occurs normally during osteogenesis, luteinisation and the development of the embryo, and in pathological states such as chronic inflammation, certain immune reactions and neoplasia. Furthermore, solid tumours have been reported to secrete a diffusible factor which promotes the directional growth of new capillaries towards a growing tumour. Two events required for the formation of a new capillary in response to an angiogenesis factor in vivo are the migration and subsequent proliferation of capillary endothelial cells. Progress in purifying angiogenesis factors and studying their action has been hindered, however, by the lack of quantitative in vitro assays for capillary cell migration and proliferation. Recently, we have been able to isolate clonal cell lines of bovine capillary endothelial cells that can be maintained in long-term culture using tumour-conditioned growth medium. I now report a quantitative in vitro assay for endothelial cell migration based on the phagokinetic track assay of Albrecht-Buehler. The evidence presented here demonstrates that tumour-derived factors stimulate the migration of capillary endothelial cells whereas the same factors have no effect on the migration of aortic endothelial cells.