Recent discoveries of endogenous negative regulators of angiogenesis, thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor, all associated with neovascularized tumours, suggest a new paradigm of tumorigenesis. It is now helpful to think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth. The extent to which the negative regulators are decreased during this switch may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.

avascular site, the cornea of a rabbit eye (Gimbrone et al., 1972). The implants attracted new capillaries that Boston, Massachusetts 02115 ‡ Depts. of Surgery and Cell Biology grew in from the limbus to vascularize the expanding tumor mass. If the capillaries were physically prevented Harvard Medical School Boston, Massachusetts 02115 from reaching the implant or were inhibited from undergoing angiogenesis, tumor growth was dramatically impaired, restricting the tumor nodule to a diameter of approximately 0.4 mm. Subsequent experiments have

The number of microvessels per 200x field in the areas of most intensive neovascularization in an invasive breast carcinoma may be an independent predictor of metastatic disease either in axillary lymph nodes or at distant sites (or both). Assessment of tumor angiogenesis may therefore prove valuable in selecting patients with early breast carcinoma for aggressive therapy.