Angiogenesis is an early event in the generation of myc-induced lymphomas.
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).
Brandvold
K A
KA
Fred Hutchinson Cancer Research Center, Seattle, Washington, WA 98109-1024, USA.
Neiman
P
P
Ruddell
A
A
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism; D002060:Bursa of Fabricius / Q000098:blood supply* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002642:Chick Embryo; D017077:Culture Media, Conditioned; D016259:Genes, myc; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned