In other words, tumors might exist for an extended period of time in a previously unrecognized pre-vascular phase where they do not yet have their own blood supply. The tumor is able to grow beyond this size by eliciting new blood vessels from surrounding tissue, and the secretion of TAF by the tumor is part of the mechanism by which this occurs. Therefore, if the action of TAF could be blocked, the tumor might be arrested at this small size. In a 1987 review article published in Science , Folkman described a number of growth factors which stimulate angiogenesis at the cellular level which had by that time been isolated from brain and eye tissue, as well as from cartilage. The discovery that many of these factors had an affinity for heparin greatly facilitated the isolation of additional growth factors from a wide variety of normal tissues.
Tumors induce angiogenesis almost continuously until the neoplasm is eliminated or the host dies.
None of the normal host mechanisms for controlling angiogenesis seem to limit tumor angiogenesis . In the mid-1970s Folkman elaborated his hypothesis about the nature of tumor angiogenesis in a series of articles published in the Annals of Internal Medicine, New England Journal of Medicine, and Scientific American. When tumor cells are inoculated into animals, the tumors vascularize so quickly that the avascular phase is not perceptible. The time required for capillaries to infiltrate a tumor graft can vary from 72 hours to 8 weeks. However, once capillaries have penetrated the tumor in the vascular phase, rapid tumor growth begins within 24 hours.