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Thromb Haemost 2003; 90(04): 570-576
DOI: 10.1160/TH03-03-0188
Review Article
Schattauer GmbH

Role of c-kit/Kit ligand signaling in regulating vasculogenesis

Beate Heissig
1   Department of Transfusion Medicine/Stem Cell Biology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
,
Zena Werb
2   Department of Anatomy, University of California, San Francisco, California, USA
,
Shahin Rafii
3   Department of Hematology-Oncology, Cornell University Medical College, New York, USA
,
Koichi Hattori
1   Department of Transfusion Medicine/Stem Cell Biology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
› Author Affiliations
Further Information

Publication History

Received 28 March 2003

Accepted after revision 21 July 2003

Publication Date:
05 December 2017 (online)

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Summary

Mobilization into peripheral blood of bone marrow-derived cells including hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs), is regulated by chemokines/cytokines. These cells can contribute to the formation of new blood vessels (vasculogenesis) under pathological conditions including atherosclerosis, wound healing and tumor growth. We will review how these cells are mobilized into circulation, and supplied to the sites, where vessel formation is needed (i.e. ischemic tissue or tumor bed).We will give evidence that matrix metalloproteinase-9 mediated Kit ligand (Stem cell factor) processing is essential for cell mobilization induced by chemo-/cyto-kines, like vascular endothelial growth factor (VEGF), Placental growth factor (PlGF), stromal cell derived factor-1 (SDF-1). These studies may provide the basis for the development of new therapeutic strategies for vascular diseases through targeting kit ligand mediated mobilization and homing of bone marrow-derived progenitor cells for cell therapy and cancer therapy.

This publication was partially financed by Serono Foundation for the Advancement of Medical Science. Financial support: This work was supported by a grant from the Japanese Society for the Promotion of Science (B.H.) and by funds from the National Institutes of Health (CA 72006 and AR46238 to ZW). Part of this paper was originally presented at the 2nd International Workshop on New Therapeutic Targets in Vascular Biology from February 6-9, 2003 in Geneva, Switzerland.

Keywords

Matrix metalloproteinase-9 - endothelial progenitor cells - tyrosine kinase receptor - stem cells - vasculogenesis
 

  • References

  • 1 Carmeliet P. Angiogenesis in health and disease. Nat Med 2003; 9 (06) 653-60.
    CrossrefPubMedGoogle Scholar
  • 2 Asahara T, Murohara T, Sullivan A. et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275 5302 964-7.
    CrossrefPubMedGoogle Scholar
  • 3 Takahashi T, Kalka C, Masuda H. et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 1999; 5 (04) 434-8.
    CrossrefPubMedGoogle Scholar
  • 4 Tateishi-Yuyama E, Matsubara H, Murohara T. et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 2002; 360 9331 427-35.
    CrossrefPubMedGoogle Scholar
  • 5 Shimizu K, Sugiyama S, Aikawa M. et al. Host bone-marrow cells are a source of donor intimal smooth- muscle-like cells in murine aortic transplant arteriopathy. Nat Med 2001; 7 (06) 738-41.
    CrossrefPubMedGoogle Scholar
  • 6 Lyden D, Hattori K, Dias S. et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001; 7 (11) 1194-201.
    CrossrefPubMedGoogle Scholar
  • 7 Gussoni E, Soneoka Y, Strickland CD. et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 1999; 401 6751 390-4.
    PubMedGoogle Scholar
  • 8 Asahara T, Masuda H, Takahashi T. et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999; 85 (03) 221-8.
    CrossrefPubMedGoogle Scholar
  • 9 Heissig B, Hattori K, Dias S. et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002; 109 (05) 625-37.
    CrossrefPubMedGoogle Scholar
  • 10 Lin Y, Weisdorf DJ, Solovey A. et al. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 2000; 105 (01) 71-7.
    CrossrefPubMedGoogle Scholar
  • 11 Rafii S, Heissig B, Hattori K. Efficient mobilization and recruitment of marrow-derived endothelial and hematopoietic stem cells by adenoviral vectors expressing angiogenic factors. Gene Ther 2002; 9 (10) 631-41.
    CrossrefPubMedGoogle Scholar
  • 12 Rafii S, Lyden D, Benezra R. et al. Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy?. Nat Rev Cancer 2002; 2 (11) 826-35.
    CrossrefPubMedGoogle Scholar
  • 13 Rehman J, Li J, Orschell CM, March KL. Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation 2003; 107 (08) 1164-9.
    CrossrefPubMedGoogle Scholar
  • 14 Kessinger A, Armitage JO, Landmark JD. et al. Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy. Blood 1988; 71 (03) 723-7.
    PubMedGoogle Scholar
  • 15 Abkowitz JL, Robinson AE, Kale S. et al. The mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure. Blood 2003; 24: 24
    PubMedGoogle Scholar
  • 16 Coussens LM, Tinkle CL, Hanahan D, Werb Z. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 2000; 103 (03) 481-90.
    CrossrefPubMedGoogle Scholar
  • 17 Vajkoczy P, Blum S, Lamparter M. et al. Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis. J Exp Med 2003; 197 (12) 1755-65.
    CrossrefPubMedGoogle Scholar
  • 18 Leung DW, Cachianes G, Kuang WJ. et al. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989; 246 4935 1306-9.
    CrossrefPubMedGoogle Scholar
  • 19 Flamme I, Breier G, Risau W. Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (flk-1) are expressed during vasculogenesis and vascular differentiation in the quail embryo. Dev Biol 1995; 169 (02) 699-712.
    CrossrefPubMedGoogle Scholar
  • 20 Fong GH, Rossant J, Gertsenstein M. et al. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995; 376 6535 66-70.
    CrossrefPubMedGoogle Scholar
  • 21 Ferrara N, Carver-Moore K, Chen H. et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996; 380 6573 439-42.
    CrossrefPubMedGoogle Scholar
  • 22 Pepper MS, Mandriota SJ. Regulation of vascular endothelial growth factor receptor-2 (Flk-1) expression in vascular endothelial cells. Exp Cell Res 1998; 241 (02) 414-25.
    CrossrefPubMedGoogle Scholar
  • 23 Hattori K, Dias S, Heissig B. et al. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med 2001; 193 (09) 1005-14.
    CrossrefPubMedGoogle Scholar
  • 24 Kabrun N, Buhring HJ, Choi K. et al. Flk-1 expression defines a population of early embryonic hematopoietic precursors. Development 1997; 124 (10) 2039-48.
    PubMedGoogle Scholar
  • 25 Hattori K, Heissig B, Wu Y. et al. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 2002; 8 (08) 841-9.
    CrossrefPubMedGoogle Scholar
  • 26 Shintani S, Murohara T, Ikeda H. et al. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 2001; 103 (23) 2776-9.
    CrossrefPubMedGoogle Scholar
  • 27 Wright DE, Cheshier SH, Wagers AJ. et al. Cyclophosphamide/granulocyte colony-stimulating factor causes selective mobilization of bone marrow hematopoietic stem cells into the blood after M phase of the cell cycle. Blood 2001; 97 (08) 2278-85.
    CrossrefPubMedGoogle Scholar
  • 28 To LB, Haylock DN, Simmons PJ. et al. The biology and clinical uses of blood stem cells. Blood 1997; 89 (07) 2233-58.
    PubMedGoogle Scholar
  • 29 Hattori K, Heissig B, Rafii S. The regulation of hematopoietic stem cell and progenitor mobilization by chemokine SDF-1. Leuk Lymphoma 2003; 44 (04) 575-82.
    CrossrefPubMedGoogle Scholar
  • 30 Gupta SK, Lysko PG, Pillarisetti K. et al. Chemokine receptors in human endothelial cells. Functional expression of CXCR4 and its transcriptional regulation by inflammatory cytokines. J Biol Chem 1998; 273 (07) 4282-7.
    CrossrefPubMedGoogle Scholar
  • 31 Volin MV, Joseph L, Shockley MS. et al. Chemokine receptor CXCR4 expression in endothelium. Biochem Biophys Res Commun 1998; 242 (01) 46-53.
    CrossrefPubMedGoogle Scholar
  • 32 Feil C, Augustin HG. Endothelial cells differentially express functional CXC-chemokine receptor-4 (CXCR-4/fusin) under the control of autocrine activity and exogenous cytokines. Biochem Biophys Res Commun 1998; 247 (01) 38-45.
    CrossrefPubMedGoogle Scholar
  • 33 Tachibana K, Hirota S, Iizasa H. et al. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature 1998; 393 6685 591-4.
    CrossrefPubMedGoogle Scholar
  • 34 Hattori K, Heissig B, Tashiro K. et al. Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood 2001; 97 (11) 3354-60.
    CrossrefPubMedGoogle Scholar
  • 35 Petit I, Szyper-Kravitz M, Nagler A. et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 2002; 3 (07) 687-94.
    CrossrefPubMedGoogle Scholar
  • 36 Fibbe WE, Pruijt JF, van Kooyk Y. et al. The role of metalloproteinases and adhesion molecules in interleukin-8-induced stem-cell mobilization. Semin Hematol 2000; 37 1 Suppl 2 19-24.
    PubMedGoogle Scholar
  • 37 Natori T, Sata M, Washida M. et al. G-CSF stimulates angiogenesis and promotes tumor growth: potential contribution of bone marrow-derived endothelial progenitor cells. Biochem Biophys Res Commun 2002; 297 (04) 1058-61.
    CrossrefPubMedGoogle Scholar
  • 38 Thomas J, Liu F, Link DC. Mechanisms of mobilization of hematopoietic progenitors with granulocyte colony-stimulating factor. Curr Opin Hematol 2002; 9 (03) 183-9.
    CrossrefPubMedGoogle Scholar
  • 39 Ribatti D, Presta M, Vacca A. et al. Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood 1999; 93 (08) 2627-36.
    PubMedGoogle Scholar
  • 40 Heeschen C, Aicher A, Lehmann R. et al. Erythropoietin is a potent physiological stimulus for endothelial progenitor cell mobilization. Blood 2003; 17: 17
    PubMedGoogle Scholar
  • 41 Brizzi MF, Battaglia E, Montrucchio G. et al. Thrombopoietin stimulates endothelial cell motility and neoangiogenesis by a platelet-activating factor-dependent mechanism. Circ Res 1999; 84 (07) 785-96.
    CrossrefPubMedGoogle Scholar
  • 42 Aicher A, Brenner W, Zuhayra M. et al. Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling. Circulation 2003; 107 (16) 2134-9.
    CrossrefPubMedGoogle Scholar
  • 43 Yamaguchi J, Kusano KF, Masuo O. et al. Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 2003; 107 (09) 1322-8.
    CrossrefPubMedGoogle Scholar
  • 44 Orlic D, Kajstura J, Chimenti S. et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410 6829 701-5.
    CrossrefPubMedGoogle Scholar
  • 45 Kocher AA, Schuster MD, Szabolcs MJ. et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 2001; 7 (04) 430-6.
    CrossrefPubMedGoogle Scholar
  • 46 Sata M, Saiura A, Kunisato A. et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med 2002; 8 (04) 403-9.
    CrossrefPubMedGoogle Scholar
  • 47 Carmeliet P, Moons L, Luttun A. et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 2001; 7 (05) 575-83.
    CrossrefPubMedGoogle Scholar
  • 48 Ichiyama K, Yokoyama-Kumakura S, Tanaka Y. et al. A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity. Proc Natl Acad Sci U S A 2003; 100 (07) 4185-90.
    CrossrefPubMedGoogle Scholar
  • 49 Bergers G, Brekken R, McMahon G. et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2000; 2 (10) 737-44.
    CrossrefPubMedGoogle Scholar
  • 50 McQuibban GA, Butler GS, Gong JH. et al. Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1. J Biol Chem 2001; 276 (47) 43503-8.
    CrossrefPubMedGoogle Scholar
  • 51 Ito A, Mukaiyama A, Itoh Y, Nagase H. et al. Degradation of interleukin 1beta by matrix metalloproteinases. J Biol Chem 1996; 271 (25) 14657-60.
    CrossrefPubMedGoogle Scholar
  • 52 Heissig B, Hattori K, Friedrich M. et al. Angiogenesis: vascular remodeling of the extracellular matrix involves metalloproteinases. Curr Opin Hematol 2003; 10 (02) 136-41.
    CrossrefPubMedGoogle Scholar
  • 53 Boesiger J, Tsai M, Maurer M. et al. Mast cells can secrete vascular permeability factor/ vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of fc epsilon receptor I expression. J Exp Med 1998; 188 (06) 1135-45.
    CrossrefPubMedGoogle Scholar
  • 54 Zhang W, Stoica G, Tasca SI. et al. Modulation of tumor angiogenesis by stem cell factor. Cancer Res 2000; 60 (23) 6757-62.
    PubMedGoogle Scholar
  • 55 Turner AM, Zsebo KM, Martin F. et al. Nonhematopoietic tumor cell lines express stem cell factor and display c-kit receptors. Blood 1992; 80 (02) 374-81.
    PubMedGoogle Scholar
  • 56 Demetri GD, von Mehren M, Blanke CD. et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347 (07) 472-80.
    CrossrefPubMedGoogle Scholar
  • 57 Bergers G, Song S, Meyer-Morse N. et al. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 2003; 111 (09) 1287-95.
    CrossrefPubMedGoogle Scholar
  • 58 Davidoff AM, Ng CY, Brown P. et al. Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice. Clin Cancer Res 2001; 7 (09) 2870-9.
    PubMedGoogle Scholar
  • 59 De Palma M, Venneri MA, Roca C. et al. Targeting exogenous genes to tumor angio-genesis by transplantation of genetically modified hematopoietic stem cells. Nat Med 2003; 9 (06) 789-95.
    CrossrefPubMedGoogle Scholar