In vivo administration of vascular endothelial growth factor (VEGF) and its antagonist, soluble neuropilin-1, predicts a role of VEGF in the progression of acute myeloid leukemia in vivo

作者: Gunter Schuch , Marcelle Machluf , Georg Bartsch , Masashi Nomi , Henri Richard

DOI: 10.1182/BLOOD.V100.13.4622

关键词: ImmunologyVascular endothelial growth factorMedicineCancer researchMyeloid leukemiaNeuropilin 1LeukemiaVascular endothelial growth factor ANeovascularizationIn vivoBone marrow

摘要: Recent findings implied that the progression of hematologic malignancies, like solid tumors, is dependent on neovascularization. studies patients with acute myeloid leukemia (AML) showed increased levels leukocyte-associated vascular endothelial growth factor (VEGF) and neovascularization bone marrow. Murine (32D, M1) human (HEL, U937, UKE-1) leukemic cell lines freshly isolated cells were analyzed for expression VEGF receptor mRNA. The receptors KDR neuropilin-1 (NRP-1) was detected in these cells. In a murine chloroma model, delivery VEGF165using microencapsulation technology resulted enhanced tumor vascularization, whereas treatment antagonist soluble NRP-1 (sNRP-1) inhibited angiogenesis growth. systemic survival mice injected adenovirus (Ad) encoding Fc-sNRP-1 (sNRP-1 dimer) significantly prolonged as compared Ad-LacZ. Further analyses reduction circulating infiltration liver spleen well marrow cellularity. Taken together, results demonstrate angiogenic factors such promote AML vivo. use antagonists an antiangiogenesis approach offers potential AML. Finally, our novel vivo drug model may be useful testing activities other peptide antiangiogenic factors.

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