Bone marrow is a reservoir for proangiogenic myelomonocytic cells but not endothelial cells in spontaneous tumors

被引:41
作者
Dudley, Andrew C. [1 ,2 ]
Udagawa, Taturo [1 ,2 ]
Melero-Martin, Juan M. [1 ,3 ]
Shih, Shou-Ching [4 ]
Curatolo, Adam [1 ,2 ]
Moses, Marsha A. [1 ,2 ]
Klagsbrun, Michael [1 ,2 ,5 ]
机构
[1] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA
[2] Childrens Hosp Boston, Vasc Biol Program, Boston, MA USA
[3] Childrens Hosp Boston, Dept Cardiac Surg, Boston, MA USA
[4] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA
[5] Childrens Hosp Boston, Dept Pathol, Boston, MA USA
基金
美国国家卫生研究院;
关键词
PROGENITOR CELLS; MOUSE MODEL; ANGIOGENESIS; CONTRIBUTE; GROWTH; LYMPHANGIOGENESIS; MACROPHAGES; PRECURSORS; MONOCYTES;
D O I
10.1182/blood-2010-02-271122
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The hypothesis that bone marrow-derived, circulating endothelial cells incorporate into tumor blood vessels is unresolved. We have measured the numbers of bone marrow-derived versus resident endothelial cells in spontaneous prostate cancers during different stages of tumor progression and in age-matched normal prostates. Bone marrow-derived endothelial cells were rare in dysplasia and in well differentiated cancers representing between 0 and 0.04% of the total tumor mass. Instead, approximately 99% of all tumor-associated bone marrow-derived cells were CD45(+) hematopoietic cells, including GR-1(+), F4-80(+), and CD11b(+) myeloid cells. Similar to peripheral blood mononuclear cells, these tumor-associated myeloid cells expressed matrix metalloproteinases (MMPs), con-sistent with their proposed catalytic role during tumor angiogenesis. Furthermore, freshly isolated CD11b(+) cells stimulated tumor endothelial cell cord formation by 10-fold in an in vitro angiogenesis assay. The bone marrow is, therefore, a reservoir for cells that augment tumor angiogenesis, but the tumor endothelium is derived primarily from the local environment. (Blood. 2010; 116(17): 3367-3371)
引用
收藏
页码:3367 / 3371
页数:5
相关论文
共 25 条
  • [11] Utilization of bone marrow-derived endothelial cell precursors in spontaneous prostate tumors varies with tumor grade
    Li, HQ
    Gerald, WL
    Benezra, R
    [J]. CANCER RESEARCH, 2004, 64 (17) : 6137 - 6143
  • [12] Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth
    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, ZP
    Hackett, NR
    Crystal, RG
    Moore, MAS
    Hajjar, KA
    Manova, K
    Benezra, R
    Rafii, S
    [J]. NATURE MEDICINE, 2001, 7 (11) : 1194 - 1201
  • [13] Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis
    Nozawa, Hiroaki
    Chiu, Christopher
    Hanahan, Douglas
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (33) : 12493 - 12498
  • [14] Contribution of bone marrow-derived endothelial cells to human tumor vasculature
    Peters, BA
    Diaz, LA
    Polyak, K
    Meszler, L
    Romans, K
    Guinan, EC
    Antin, JH
    Myerson, D
    Hamilton, SR
    Vogelstein, B
    Kinzler, KW
    Lengauer, C
    [J]. NATURE MEDICINE, 2005, 11 (03) : 261 - 262
  • [15] A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships
    Pucci, Ferdinando
    Venneri, Mary Anna
    Biziato, Daniela
    Nonis, Alessandro
    Moi, Davide
    Sica, Antonio
    Di Serio, Clelia
    Naldini, Luigi
    De Palma, Michele
    [J]. BLOOD, 2009, 114 (04) : 901 - 914
  • [16] Bone marrow-derived circulating endothelial precursors do not contribute to vascular endothelium and are not needed for tumor growth
    Purhonen, Susanna
    Palm, Jarmo
    Rossi, Derrick
    Kaskenpaa, Nina
    Rajantie, Iiro
    Yla-Herttuala, Seppo
    Alitalo, Kari
    Weissman, Irving L.
    Salven, Petri
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (18) : 6620 - 6625
  • [17] Lymphatic endothelium-specific hyaluronan receptor LYVE-1 is expressed by stabilin-1+, F4/80+, CD11b+ macrophages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro:: implications for the assessment of lymphangiogenesis
    Schledzewski, K
    Falkowski, M
    Moldenhauer, G
    Metharom, P
    Kzhyshkowska, J
    Ganss, R
    Demory, A
    Falkowska-Hansen, B
    Kurzen, H
    Ugurel, S
    Geginat, G
    Arnold, B
    Goerdt, S
    [J]. JOURNAL OF PATHOLOGY, 2006, 209 (01) : 67 - 77
  • [18] Chemokines direct endothelial progenitors into tumor neovessels
    Spring, H
    Schüler, T
    Arnold, B
    Hämmerling, GJ
    Ganss, R
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (50) : 18111 - 18116
  • [19] Endothelial progenitor cells do not contribute to tumor endothelium in primary and metastatic tumors
    Wickersheim, Anke
    Kerber, Mark
    de Miguel, Lourdes Sanchez
    Plate, Karl H.
    Machein, Marcia Regina
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2009, 125 (08) : 1771 - 1777
  • [20] Expansion of myeloid immune suppressor Gr+CD11b+cells in tumor-bearing host directly promotes tumor angiogenesis
    Yang, L
    DeBusk, LM
    Fukuda, K
    Fingleton, B
    Green-Jarvis, B
    Shyr, Y
    Matrisian, LM
    Carbone, DP
    Lin, PC
    [J]. CANCER CELL, 2004, 6 (04) : 409 - 421