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

Citation
D. Lyden et al., Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth, NAT MED, 7(11), 2001, pp. 1194-1201
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
NATURE MEDICINE
ISSN journal
1078-8956 → ACNP
Volume
7
Issue
11
Year of publication
2001
Pages
1194 - 1201
Database
ISI
SICI code
1078-8956(200111)7:11<1194:IROBEA>2.0.ZU;2-E
Abstract
The role of bone marrow (BM)-derived precursor cells in tumor angiogenesis is not known, We demonstrate here that tumor angiogenesis is associated wit h recruitment of hematopoietic and circulating endothelial precursor cells (CEPs). We used the angiogenic defective, tumor resistant ld-mutant mice to show that transplantation of wild-type BM or vascular endothelial growth f actor (VEGF)-mobilized stem cells restore tumor angiogenesis and growth. We detected donor-derived CEPs throughout the neovessels of tumors and Matrig el-plugs in an Id1(+/-)Id3(-/-) host, which were associated with VEGF-recep tor-1-positive (VEGFR1(+))myeloid cells. The angiogenic defect in ld-mutant mice was due to impaired VEGF-driven mobilization of VEGFR2(+) CEPs and im paired proliferation and incorporation of VEGFR1(+) cells. Although targeti ng of either VEGFR1 or VEGFR2 alone partially blocks the growth of tumors, inhibition of both VEGFR1 and VEGFR2 was necessary to completely ablate tum or growth. These data demonstrate that recruitment of VEGF-responsive BM-de rived precursors is necessary and sufficient for tumor angiogenesis and sug gest new clinical strategies to block tumor growth.