By RICHARD G . AZIZKHAN , JANE CLIFFORD AZIZKHAN , BRUCE R . ZETTER , : I : AND JUDAH FOLKMAN

It is now recognized that angiogenesis, the induction of capillary proliferation, is important for the continued growth of solid tumors (1-3). Kessler et al. (4) reported that mast cells assemble at a tumor site before the ingrowth of new capillaries; it was proposed that mast cells may play a role in tumor angiogenesis. Mast cells are also found in increased numbers in other pathologic states associated with angiogenesis, such as psoriasis (5, 6), chronic inflammation (7, 8), and immune rejection (9, 10). However, the exact function of the mast cells in angiogenesis is not understood. Previously, Ausprunk and Folkman (11) reported that capillary endothelial cell migration was one of the major components of the growing capillary sprouts that arise in angiogenesis. After bovine capillary endothelial cells were cloned and carried in long-term culture (12) in this laboratory, Zetter (13) developed a quanti tat ive assay in vitro for measuring the migration of these cells. In this assay, bovine capillary endothelial cells were plated sparsely on glass cover slips coated with colloidal gold so that their migration generated a phagokinetic track, the area of which could be measured accurately. We now report that mast cells release a factor that stimulates migration of capillary endothelial cells. We have investigated the effect of isolated mast cell products on bovine capillary endothelial cell migration, and we demonstrate that heparin is the mast cell factor responsible for capillary endothelial cell migration in vitro.