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

David Lyden, Koichi Hattori, Sergio Dias, Carla Costa, Pamela Blaikie, Linda Butros, Amy Chadburn, Beate Heissig, Willy Marks, Larry Witte, Yan Wu, Daniel Hicklin, Zhenping Zhu, Neil R. Hackett, Ronald Crystal, Malcolm A S Moore, Katherine A. Hajjar, Katia Manova, Robert Benezra, Shahin Rafii

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1194-1201
Number of pages8
JournalNature Medicine
Volume7
Issue number11
DOIs
Publication statusPublished - 26 Nov 2001
Externally publishedYes

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Tumors
Bone
Bone Marrow
Growth
Neoplasms
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1
Neoplastic Stem Cells
Myeloid Cells
Bone Marrow Transplantation
Stem cells
Endothelial Cells
Defects

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. / Lyden, David; Hattori, Koichi; Dias, Sergio; Costa, Carla; Blaikie, Pamela; Butros, Linda; Chadburn, Amy; Heissig, Beate; Marks, Willy; Witte, Larry; Wu, Yan; Hicklin, Daniel; Zhu, Zhenping; Hackett, Neil R.; Crystal, Ronald; Moore, Malcolm A S; Hajjar, Katherine A.; Manova, Katia; Benezra, Robert; Rafii, Shahin.

In: Nature Medicine, Vol. 7, No. 11, 26.11.2001, p. 1194-1201.

Research output: Contribution to journalArticle

Lyden, D, Hattori, K, Dias, S, Costa, C, Blaikie, P, Butros, L, Chadburn, A, Heissig, B, Marks, W, Witte, L, Wu, Y, Hicklin, D, Zhu, Z, Hackett, NR, Crystal, R, Moore, MAS, Hajjar, KA, Manova, K, Benezra, R & Rafii, S 2001, 'Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth', Nature Medicine, vol. 7, no. 11, pp. 1194-1201. https://doi.org/10.1038/nm1101-1194
Lyden, David ; Hattori, Koichi ; Dias, Sergio ; Costa, Carla ; Blaikie, Pamela ; Butros, Linda ; Chadburn, Amy ; Heissig, Beate ; Marks, Willy ; Witte, Larry ; Wu, Yan ; Hicklin, Daniel ; Zhu, Zhenping ; Hackett, Neil R. ; Crystal, Ronald ; Moore, Malcolm A S ; Hajjar, Katherine A. ; Manova, Katia ; Benezra, Robert ; Rafii, Shahin. / Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. In: Nature Medicine. 2001 ; Vol. 7, No. 11. pp. 1194-1201.
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AU - Hicklin, Daniel

AU - Zhu, Zhenping

AU - Hackett, Neil R.

AU - Crystal, Ronald

AU - Moore, Malcolm A S

AU - Hajjar, Katherine A.

AU - Manova, Katia

AU - Benezra, Robert

AU - Rafii, Shahin

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