Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth Journal Article
| Authors: | Lyden, D.; Hattori, K.; Dias, S.; Costa, C.; Blaikie, P.; Butros, L.; Chadburn, A.; Heissig, B.; Mark, W.; Witte, L.; Wu, Y.; Hicklin, D.; Zhu, Z.; Hackett, N. R.; Crystal, R. G.; Moore, M. A. S.; Hajjar, K. A.; Manova, K.; Benezra, R.; Rafii, S. |
| Article Title: | Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth |
| Abstract: | 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. |
| Keywords: | vasculotropin; mutation; dna-binding proteins; proto-oncogene proteins; histopathology; nonhuman; receptors, vascular endothelial growth factor; animal cell; mouse; animals; mice; mice, knockout; animal tissue; vasculotropin receptor; neoplasm proteins; animal experiment; animal model; mice, mutant strains; stem cell transplantation; hematopoietic stem cell transplantation; neovascularization, pathologic; mice, inbred c57bl; carcinogenesis; animalia; transcription factors; stem cell; endothelium cell; endothelium, vascular; hematopoietic cell; hematopoietic stem cells; neoplasms, experimental; inhibitor of differentiation protein 1; receptor protein-tyrosine kinases; tumor growth; bone marrow transplantation; vascular endothelial growth factor receptor-1; repressor proteins; neovascularization (pathology); receptors, growth factor; inhibitor of differentiation proteins; neutralizing antibody; mobilization; neutralization tests; priority journal; article |
| Journal Title: | Nature Medicine |
| Volume: | 7 |
| Issue: | 11 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2001-11-01 |
| Start Page: | 1194 |
| End Page: | 1201 |
| Language: | English |
| DOI: | 10.1038/nm1101-1194 |
| PUBMED: | 11689883 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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