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

Abstract

Angiogenesis was identified as an early consequence of myc gene overexpression 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 metastatic lymphoma. Immunohistochemical studies of the effects of increased c-myc or v-myc overexpression revealed early angiogenesis within myc-transformed bursal follicles, which persisted in lymphomas and metastases. Abnormal vessel growth was consistently detected within 13 days after transplantation of a few myc-overexpressing progenitors into ablated bursal follicles, suggesting 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 endothelium in vitro, while media from B cells expressing low myc levels showed little effect. Moreover, ectopic myc overexpression in the low myc B cell lines increased production of the endothelial growth activity, indicating that myc induces secretion of angiogenic factors from B cells. These findings demonstrate that myc overexpression in lymphocytes generates an angiogenic phenotype in vitro as well as in vivo. Oncogene (2000).