An in vivo function for the transforming Myc protein: Elicitation of the angiogenic phenotype

The ability of neoplastic cells to recruit blood vasculature is crucial to their survival in the host organism. However, the evidence linking dominant oncogenes to the angiogenic switch remains incomplete. We demonstrate here that Myc, an oncoprotein implicated in many human malignancies, stimulates neovascularization, As an experimental model, we used Rat-1A fibroblasts t hat form vascular tumors upon transformation by Myc in immunocompromised mi ce. Our previous work and the use of neutralizing antibodies reveal that in these cells, the angiogenic switch is achieved via down-modulation of thro mbospondin-1, a secreted inhibitor of angiogenesis, whereas the levels of v ascular endothelial growth factor, a major activator of angiogenesis, remai n high and unaffected by Myc, Consistent with this finding, overexpression of Myc confers upon the conditioned media the ability to promote migration of adjacent endothelial cells in vitro and corneal neovascularization in vi vo. Furthermore, mobilization of estrogen-dependent Myc in vivo with the ap propriate steroid provokes neovascularization of cell implants embedded in Matrigel, These data suggest that Myc is fully competent to trigger the ang iogenic switch in vivo and that secondary events may not be required for ne ovascularization of Myc-induced tumors.