Angiogenesis is an early event in the generation of myc-induced lymphomas

Angiogenesis was identified as an early consequence of myc gene overexpress ion in two models of retroviral lymphomagenesis. Avian leukosis virus (ALV) induces bursal lymphoma in chickens after proviral c-myc gene integration, while the HB-1 retrovirus carries a v-myc oncogene and also induces metast atic lymphoma. Immunohistochemical studies of the effects of increased c-my c or v-myc overexpression revealed early angiogenesis within myc-transforme d bursal follicles, which persisted in lymphomas and metastases. Abnormal v essel growth was consistently detected within 13 days after transplantation of a few myc-overexpressing progenitors into ablated bursal follicles, sug gesting that these angiogenic changes may support the initial expansion of tumor precursors, as well as later stage lymphomagenesis, Conditioned media from myc-overexpressing B cell lines promoted proliferation of vascular en dothelium in vitro, while media from B cells expressing low myc levels show ed little effect. Moreover, ectopic myc overexpression in the low myc B cel l lines increased production of the endothelial growth activity, indicating that myc induces secretion of angiogenic factors from B cells. These findi ngs demonstrate that myc overexpression in lymphocytes generates an angioge nic phenotype in vitro as well as in vivo.