Angiogenesis and cancer metastasis

The growth and spread of neoplasms depends on the establishment of an adequ ate blood supply; that is, angiogenesis. The onset of angiogenesis involves a change in the local equilibrium between proangiogenic and antiangiogenic regulators that are produced by tumor cells, surrounding stromal cells, an d infiltrating leukocytes. In most normal tissues, factors that inhibit ang iogenesis predominate, whereas in rapidly dividing tissues, the balance of angiogenic molecules favors stimulation of the process. A potent inhibitor of angiogenesis is interferon-alpha or -beta, shown to down-regulate transc ription and protein production of basic fibroblast growth factor, collagena se type IV, and interleukin-8. The daily systemic administration of low (bu t not high) dose of interferon-alpha can produce significant inhibition of angiogenesis and, hence, regression of human tumors implanted orthotopicall y in nude mice. The recent elucidation of the interaction among proangiogen ic molecules during physiological processes and the apparent disruption of this balance in neoplasia should allow the design of potent and antiangioge nic therapies against primary cancers and metastases.