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Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth

Title
Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth
Type
Article in International Scientific Journal
Year
2001
Authors
David Lyden
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Koichi Hattori
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Sérgio Dias
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Carla Costa
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Shahin Rafii
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Journal
Title: Nature MedicineImported from Authenticus Search for Journal Publications
Vol. 11 No. 7
Pages: 1194-1201
ISSN: 1078-8956
Publisher: Springer Nature
Scientific classification
CORDIS: Health sciences
Other information
Abstract (EN): The role of bone marrow (BM)-derived precursor cells in tumor angiogenesis is not known. We demonstrate here that tumor angiogenesis is associated with recruitment of hematopoietic and circulating endothelial precursor cells (CEPs). We used the angiogenic defective, tumor resistant Id-mutant mice to show that transplantation of wild-type BM or vascular endothelial growth factor (VEGF)-mobilized stem cells restore tumor angiogenesis and growth. We detected donor-derived CEPs throughout the neovessels of tumors and Matrigel-plugs in an Id1+/–Id3–/– host, which were associated with VEGF-receptor-1–positive (VEGFR1+) myeloid cells. The angiogenic defect in Id-mutant mice was due to impaired VEGF-driven mobilization of VEGFR2+ CEPs and impaired proliferation and incorporation of VEGFR1+ cells. Although targeting of either VEGFR1 or VEGFR2 alone partially blocks the growth of tumors, inhibition of both VEGFR1 and VEGFR2 was necessary to completely ablate tumor growth. These data demonstrate that recruitment of VEGF-responsive BM-derived precursors is necessary and sufficient for tumor angiogenesis and suggest new clinical strategies to block tumor growth.
Language: Portuguese
Type (Professor's evaluation): Scientific
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