Skip to main content
SpringerLink
Log in

Homing and Differentiation of Endothelial Progenitor Cells

  • Chapter
Tumor Angiogenesis

Abstract

Endothelial progenitor cells (EPC), which presumable originate from bone marrowderived progenitor cells, circulate with the blood on mobilization from the bone marrow, and home to sites of active vessel growth, a process termed “adult vasculogenesis”. Infusion of EPC improves neovascularization in mice and in clinical trials. Several studies demonstrated that EPC contribute to tumor angiogenesis. However, the extent of endothelial incorporation and the precise mechanisms by which EPC contribute to neovessel formation are still under debate. Defining the events in progenitor cell homing and differentiation may enable novel therapeutic strategies to improve or block vascular regeneration. Homing is a multi-step cascade including the initial adhesion to activated endothelium or exposed matrix, transmigration through the endothelium, and, finally, migration and invasion into the target tissue. This review will summarize the current understanding of the molecular mechanisms mediating EPC homing.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ (2004) Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 110:3300–3305

    PubMed  Google Scholar 

  • Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau-Ihling K, Zeiher AM, Dimmeier S (2003) Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 9:1370–1376

    PubMed  CAS  Google Scholar 

  • Andreasen PA, Kjoller L, Christensen L, Duffy MJ (1997) The urokinase-type plasminogen activator system in cancer metastasis: a review. Int J Cancer 72:1–22

    PubMed  CAS  Google Scholar 

  • Annabi B, Naud E, Lee YT, Eliopoulos N, Galipeau J (2004) Vascular progenitors derived from murine bone marrow stromal cells are regulated by fibroblast growth factor and are avidly recruited by vascularizing tumors. J Cell Biochem 91:1146–1158

    PubMed  CAS  Google Scholar 

  • Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967

    PubMed  CAS  Google Scholar 

  • Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228

    PubMed  CAS  Google Scholar 

  • Askari AT, Unzek S, Popovic ZB, Goldman CK, Forudi F, Kiedrowski M, Rovner A, Ellis SG, Thomas JD, DiCorleto PE, Topol EJ, Penn MS (2003) Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 362:697–703

    PubMed  CAS  Google Scholar 

  • Basire A, Sabatier F, Ravet S, Lamy E, Mialhe A, Zabouo G, Paul P, Gurewich V, Sampol J, Dignat-George F (2006) High urokinase expression contributes to the angiogenic properties of endothelial cells derived from circulating progenitors. Thromb Haemost 95:678–688

    PubMed  CAS  Google Scholar 

  • Bazzoni G, Hemler ME (1998) Are changes in integrin affinity and conformation overemphasized? Trends Biochem Sci 23:30–34

    PubMed  CAS  Google Scholar 

  • Becker PS, Nilsson SK, Li Z, Berrios VM, Dooner MS, Cooper CL, Hsieh CC, Quesenberry PJ (1999) Adhesion receptor expression by hematopoietic cell lines and murine progenitors: modulation by cytokines and cell cycle status. Exp Hematol 27:533–541

    PubMed  CAS  Google Scholar 

  • Berchem G, Glondu M, Gleizes M, Brouillet JP, Vignon F, Garcia M, Liaudet-Coopman E (2002) Cathepsin-D affects multiple tumor progression steps in vivo: proliferation, angiogenesis and apoptosis. Oncogene 21:5951–5955

    PubMed  CAS  Google Scholar 

  • Berlin C, Bargatze RF, Campbell JJ, von Andrian UH, Szabo MC, Hasslen SR, Nelson RD, Berg EL, Erlandsen SL, Butcher EC (1995) alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 80:413–422

    PubMed  CAS  Google Scholar 

  • Biancone L, Cantaluppi V, Duo D, Deregibus MC, Torre C, Camussi G (2004) Role of L-selectin in the vascular homing of peripheral blood-derived endothelial progenitor cells. J Immunol 173:5268–5274

    PubMed  CAS  Google Scholar 

  • Carlos TM, Harlan JM (1994) Leukocyte-endothelial adhesion molecules. Blood 84:2068–2101

    PubMed  CAS  Google Scholar 

  • Carman CV, Springer TA (2003) Integrin avidity regulation: are changes in affinity and conformation underemphasized? Curr Opin Cell Biol 15:547–556

    PubMed  CAS  Google Scholar 

  • Carman CV, Springer TA (2004) A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J Cell Biol 167:377–388

    PubMed  CAS  Google Scholar 

  • Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936

    PubMed  CAS  Google Scholar 

  • Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, Capla JM, Galiano RD, Levine JP, Gurtner GC (2004) Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med 10:858–864. Epub Jul 2004

    PubMed  CAS  Google Scholar 

  • Chavakis E, Aicher A, Heeschen C, Sasaki K, Kaiser R, El Makhfi N, Urbich C, Peters T, Scharffetter-Kochanek K, Zeiher AM, Chavakis T, Dimmeier S (2005) Role of beta 2-integrins for homing and neovascularization capacity of endothelial progenitor cells. J Exp Med 201:63–72

    PubMed  CAS  Google Scholar 

  • Chavakis T, Bierhaus A, Al-Fakhri N, Schneider D, Witte S, Linn T, Nagashima M, Morser J, Arnold B, Preissner KT, Nawroth PP (2003) The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med 198:1507–1515

    PubMed  CAS  Google Scholar 

  • Chavakis T, Keiper T, Matz-Westphal R, Hersemeyer K, Sachs UJ, Nawroth PP, Preissner KT, Santoso S (2004) The junctional adhesion molecule-C promotes neutrophil transendothelial migration in vitro and in vivo. J Biol Chem 279:55602–55608

    PubMed  CAS  Google Scholar 

  • Cunningham SA, Rodriguez JM, Arrate MP, Tran TM, Brock TA (2002) JAM2 interacts with alpha4betal. Facilitation by JAM3. J Biol Chem 277:27589–27592

    PubMed  CAS  Google Scholar 

  • Dangerfield J, Larbi KY, Huang MT, Dewar A, Nourshargh S (2002) PECAM-1 (CD31) homophilic interaction up-regulates alpha6obetal on transmigrated neutrophils in vivo and plays a functional role in the ability of alpha6 integrins to mediate leukocyte migration through the perivascular basement membrane. J Exp Med 196:1201–1211

    PubMed  CAS  Google Scholar 

  • Dangerfield JP, Wang S, Nourshargh S (2005) Blockade of alpha6 integrin inhibits IL-1beta-but not TNF-alpha-in-duced neutrophil transmigration in vivo. J Leukoc Biol 77:159–165

    PubMed  CAS  Google Scholar 

  • Davis DA, Singer KE, De La Luz Sierra M, Narazaki M, Yang F, Fales HM, Yarchoan R, Tosato G (2005) Identification of carboxypeptidase N as an enzyme responsible for Cterminal cleavage of stromal cell-derived factor-1alpha in the circulation. Blood 105:4561–4568

    PubMed  CAS  Google Scholar 

  • De Falco E, Porcelli D, Torella AR, Straino S, Iachininoto MG, Orlandi A, Truffa S, Biglioli P, Napolitano M, Capogrossi MC, Pesce M (2004) SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells. Blood 104:3472–3482

    Google Scholar 

  • De la Luz Sierra M, Yang F, Narazaki M, Salvucci O, Davis D, Yarchoan R, Zhang HH, Fales H, Tosato G (2004) Differential processing of stromal-derived factor-1alpha and stromal-derived factor-1beta explains functional diversity. Blood 103:2452–2459

    Google Scholar 

  • De Palma M, Venneri MA, Naldini L (2003a) In vivo targeting of tumor endothelial cells by systemic delivery of lentiviral vectors. Hum Gene Ther 14:1193–1206

    PubMed  Google Scholar 

  • De Palma M, Venneri MA, Roca C, Naldini L (2003b) Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells. Nat Med 9:789–795

    PubMed  Google Scholar 

  • Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, Rutten H, Fichtischerer S, Martin H, Zeiher AM (2001) HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/ Akt pathway. J Clin Invest 108:391–397

    PubMed  CAS  Google Scholar 

  • Dustin ML, Bivona TG, Philips MR (2004) Membranes as messengers in T cell adhesion signaling. Nat Immunol 5:363–372

    PubMed  CAS  Google Scholar 

  • Felbor U, Dreier L, Bryant RA, Ploegh HL, Olsen BR, Mothes W (2000) Secreted cathepsin L generates endostatin from collagen XVIII. EMBO J 19:1187–1194

    PubMed  CAS  Google Scholar 

  • Ferrara N, Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438:967–974

    PubMed  CAS  Google Scholar 

  • Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell-Braxton L, Hillan KJ, Moore MW (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380:439–442

    PubMed  CAS  Google Scholar 

  • Fong GH, Rossant J, Gertsenstein M, Breitman ML (1995) Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376:66–70

    PubMed  CAS  Google Scholar 

  • Forsyth CB, Solovjov DA, Ugarova TP, Plow EF (2001) Integrin alpha(M)beta(2)-mediated cell migration to fibrinogen and its recognition peptides. J Exp Med 193:1123–1133

    PubMed  CAS  Google Scholar 

  • Fujiyama S, Amano K, Uehira K, Yoshida M, Nishiwaki Y, Nozawa Y, Jin D, Takai S, Miyazaki M, Egashira K, Imada T, Iwasaka T, Matsubara H (2003) Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells. Circ Res 93:980–989. Epub 2003 Oct 2002

    Google Scholar 

  • Garcia-Barros M, Paris F, Cordon-Cardo C, Lyden D, Rafii S, Haimovitz-Friedman A, Fuks Z, Kolesnick R (2003) Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science 300:1155–1159

    PubMed  CAS  Google Scholar 

  • Gehling UM, Ergun S, Schumacher U, Wagener C, Pantel K, Otte M, Schuch G, Schafhausen P, Mende T, Kilic N, Kluge K, Schafer B, Hossfeld DK, Fiedler W (2000) In vitro differentiation of endothelial cells from AC 133-positive progenitor cells. Blood 95:3106–3112

    PubMed  CAS  Google Scholar 

  • Grabovsky V, Feigelson S, Chen C, Bleijs DA, Peled A, Cinamon G, Baleux F, Arenzana-Seisdedos F, Lapidot T, van Kooyk Y, Lobb RR, Alon R (2000) Subsecond induction of alpha4 integrin clustering by immobilized chemokines stimulates leukocyte tethering and rolling on endothelial vascular cell adhesion molecule 1 under flow conditions. J Exp Med 192:495–506

    PubMed  CAS  Google Scholar 

  • Graf M, Baici A, Strauli P (1981) Histochemical localization of cathepsin B at the invasion front of the rabbit V2 carcinoma. Lab Invest 45:587–596

    PubMed  CAS  Google Scholar 

  • Grunewald M, Avraham I, Dor Y, Bachar-Lustig E, Itin A, Yung S, Chimenti S, Landsman L, Abramovitch R, Keshet E (2006) VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell 124:175–189

    PubMed  CAS  Google Scholar 

  • Guo Y, Chan R, Ramsey H, Li W, Xie X, Shelley WC, Martinez-Barbera JP, Bort B, Zaret K, Yoder M, Hromas R (2003) The homeoprotein Hex is required for hemangioblast differentiation. Blood 102:2428–2435. Epub 2003 Jun 2425

    Google Scholar 

  • Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109:625–637

    PubMed  CAS  Google Scholar 

  • Henderson RB, Lim LH, Tessier PA, Gavins FN, Mathies M, Perretti M, Hogg N (2001) The use of lymphocyte function-associated antigen (LFA)-l-deficient mice to determine the role of LFA-1, Mac-1, and alpha4 integrin in the inflammatory response of neutrophils. J Exp Med 194:219–226

    PubMed  CAS  Google Scholar 

  • Honey K, Nakagawa T, Peters C, Rudensky A (2002) Cathepsin L regulates CD4+ T cell selection independently of its effect on invariant chain: a role in the generation of positively selecting peptide ligands. J Exp Med 195:1349–1358

    PubMed  CAS  Google Scholar 

  • Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110:673–687

    PubMed  CAS  Google Scholar 

  • Imhof BA, Aurrand-Lions M (2004) Adhesion mechanisms regulating the migration of monocytes. Nat Rev Immunol 4:432–444

    PubMed  CAS  Google Scholar 

  • Jin DK, Shido K, Kopp HG, Petit I, Shmelkov SV, Young LM, Hooper AT, Amano H, Avecilla ST, Heissig B, Hattori K, Zhang F, Hicklin DJ, Wu Y, Zhu Z, Dunn A, Salari H, Werb Z, Hackett NR, Crystal RG, Lyden D, Rafii S (2006a) Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4(+) hemangiocytes. Nat Med 12:557–567

    PubMed  CAS  Google Scholar 

  • Jin H, Aiyer A, Su J, Borgstrom P, Stupack D, Friedlander M, Varner J (2006b) A homing mechanism for bone mar-row-derived progenitor cell recruitment to the neovasculature. J Clin Invest 116:652–662

    PubMed  CAS  Google Scholar 

  • Kalka C, Masuda H, Takahashi T, Gordon R, Tepper O, Gravereaux E, Pieczek A, Iwaguro H, Hayashi SI, Isner JM, Asahara T (2000a) Vascular endothelial growth factor(165) gene transfer augments circulating endothelial progenitor cells in human subjects. Circ Res 86:1198–1202

    PubMed  CAS  Google Scholar 

  • Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, Li T, Isner JM, Asahara T (2000b) Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 97:3422–3427

    PubMed  CAS  Google Scholar 

  • Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (2005) VEGFRl-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827

    PubMed  CAS  Google Scholar 

  • Keiper T, Al-Fakhri N, Chavakis E, Athanasopoulos AN, Isermann B, Herzog S, Saffrich R, Hersemeyer K, Bohle RM, Haendeler J, Preissner KT, Santoso S, Chavakis T (2005) The role of junctional adhesion molecule-C (JAM-C) in oxidized LDL-mediated leukocyte recruitment. FASEB J 19:2078–2080

    PubMed  CAS  Google Scholar 

  • Kinashi T (2005) Intracellular signalling controlling integrin activation in lymphocytes. Nat Rev Immunol 5:546–559

    PubMed  CAS  Google Scholar 

  • Kocher AA, Schuster MD, Bonaros N, Lietz K, Xiang G, Martens TP, Kurlanski P, Witkowski P, Boyle A, Homma S, Wang SF, Itescu S (2006) Myocardial homing and neovascularization by human bone marrow angioblasts is regulated by IL-8/ Gro CXC chemokines. J Mol Cell Cardiol 40:455–464

    PubMed  CAS  Google Scholar 

  • Krueger S, Kellner U, Buehling F and Roessner A (2001) Cathepsin L antisense oligonucleotides in a human osteosarcoma cell line: effects on the invasive phenotype. Cancer Gene Ther 8:522–528

    PubMed  CAS  Google Scholar 

  • Lapidot T (2001) Mechanism of human stem cell migration and repopulation of NOD/SCID and B2mnull NOD/SCID mice. The role of SDF-1/CXCR4 interactions. Ann NY Acad Sci 938:83–95

    PubMed  CAS  Google Scholar 

  • Laudanna C, Alon R (2006) Right on the spot. Chemokine triggering of integrin-mediated arrest of rolling leukocytes. Thromb Haemost 95:5–11

    PubMed  CAS  Google Scholar 

  • Lee S, Jilani SM, Nikolova GV, Carpizo D, Iruela-Arispe ML (2005) Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J Cell Biol 169:681–691

    PubMed  CAS  Google Scholar 

  • Lee SH, Wolf PL, Escudero R, Deutsch R, Jamieson SW, Thistlethwaite PA (2000) Early expression of angiogenesis factors in acute myocardial ischemia and infarction. N Engl J Med 342:626–633

    PubMed  CAS  Google Scholar 

  • Li H, Gerald WL, Benezra R (2004) Utilization of bone marrow-derived endothelial cell precursors in spontaneous prostate tumors varies with tumor grade. Cancer Res 64:6137–6143

    PubMed  CAS  Google Scholar 

  • Lotze MT, Tracey KJ (2005) High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 5:331–342

    PubMed  CAS  Google Scholar 

  • Luster AD, Alon R, von Andrian UH (2005) Immune cell migration in inflammation: present and future therapeutic targets. Nat Immunol 6:1182–1190

    PubMed  CAS  Google Scholar 

  • 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 RG, Moore MA, 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. Nat Med 7:1194–1201

    PubMed  CAS  Google Scholar 

  • Mason RW, Gal S, Gottesman MM (1987) The identification of the major excreted protein (MEP) from a transformed mouse fibroblast cell line as a catalytically active precursor form of cathepsin L. Biochem J 248:449–454

    PubMed  CAS  Google Scholar 

  • McEver RP (2002) Selectins: lectins that initiate cell adhesion under flow. Curr Opin Cell Biol 14:581–586

    PubMed  CAS  Google Scholar 

  • McQuibban GA, Butler GS, Gong JH, Bendall L, Power C, Clark-Lewis I, Overall CM (2001) Matrix metalloproteinase activity inactivates the CXC chemokine stromal cellderived factor-1. J Biol Chem 276:43503–43508

    PubMed  CAS  Google Scholar 

  • Muller WA (2002) Leukocyte-endothelial cell interactions in the inflammatory response. Lab Invest 82:521–533

    PubMed  CAS  Google Scholar 

  • Muller WA (2003) Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol 24:327–334

    PubMed  CAS  Google Scholar 

  • Nakagawa T, Roth W, Wong P, Nelson A, Farr A, Deussing J, Villadangos JA, Ploegh H, Peters C, Rudensky AY (1998) Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus. Science 280:450–453

    PubMed  CAS  Google Scholar 

  • Oppenheimer-Marks N, Davis LS, Bogue DT, Ramberg J, Lipsky PE (1991) Differential utilization of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of human T lymphocytes. J Immunol 147:2913–2921

    PubMed  CAS  Google Scholar 

  • Orschell-Traycoff CM, Hiatt K, Dagher RN, Rice S, Yoder MC, Srour EF (2000) Homing and engraftment potential of Sca-l(+)lin(-) cells fractionated on the basis of adhesion molecule expression and position in cell cycle. Blood 96:1380–1387

    PubMed  CAS  Google Scholar 

  • Ostermann G, Weber KS, Zernecke A, Schroder A, Weber C (2002) JAM-1 is a ligand of the beta(2) integrin LFA-1 involved in transendothelial migration of leukocytes. Nat Immunol 3:151–158

    PubMed  CAS  Google Scholar 

  • Palumbo R, Sampaolesi M, de Marchis F, Tonlorenzi R, Colombetti S, Mondino A, Cossu G, Bianchi ME (2004) Extracellular HMGB1, a signal of tissue damage, induces mesoangioblast migration and proliferation. J Cell Biol 164:441–449

    PubMed  CAS  Google Scholar 

  • Peled A, Grabovsky V, Habler L, Sandbank J, Arenzana-Seisdedos F, Petit I, Ben-Hur H, Lapidot T, Alon R (1999) The chemokine SDF-1 stimulates integrin-mediated arrest of CD34(+) cells on vascular endothelium under shear flow. J Clin Invest 104:1199–1211

    PubMed  CAS  Google Scholar 

  • Pepper MS (2001) Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol 21:1104–1117

    PubMed  CAS  Google Scholar 

  • Peters BA, Diaz LA, Polyak K, Meszler L, Romans K, Guinan EC, Antin JH, Myerson D, Hamilton SR, Vogelstein B, Kinzler KW, Lengauer C (2005) Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nat Med 11:261–262

    PubMed  CAS  Google Scholar 

  • Plow EF, Haas TA, Zhang L, Loftus J, Smith JW (2000) Ligand Binding to Integrins. J Biol Chem 275:21785–21788

    PubMed  CAS  Google Scholar 

  • Qin G, Ii M, Silver M, Wecker A, Bord E, Ma H, Gavin M, Goukassian DA, Yoon YS, Papayannopoulou T, Asahara T, Kearney M, Thorne T, Curry C, Eaton L, Heyd L, Dinesh D, Kishore R, Zhu Y, Losordo DW (2006) Functional disruption of alpha4 integrin mobilizes bone marrowderived endothelial progenitors and augments ischemic neovascularization. J Exp Med 203:153–163

    PubMed  CAS  Google Scholar 

  • Rossig L, Urbich C, Bruhl T, Dernbach E, Heeschen C, Chavakis E, Sasaki K, Aicher D, Diehl F, Seeger F, Potente M, Aicher A, Zanetta L, Dejana E, Zeiher AM, Dimmeler S (2005) Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells. J Exp Med 201:1825–1835

    PubMed  Google Scholar 

  • Roth W, Deussing J, Botchkarev VA, Pauly-Evers M, Saftig P, Hafner A, Schmidt P, Schmahl W, Scherer J, Anton-Lamprecht I, von Figura K, Paus R, Peters C (2000) Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling. FASEB J 14:2075–2086

    PubMed  CAS  Google Scholar 

  • Ruzinova MB, Schoer RA, Gerald W, Egan JE, Pandolfi PP, Rafii S, Manova K, Mittal V, Benezra R (2003) Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors. Cancer Cell 4:277–289

    PubMed  CAS  Google Scholar 

  • Salceda S, Caro J (1997) Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J Biol Chem 272:22642–22647

    PubMed  CAS  Google Scholar 

  • Santoso S, Sachs UJ, Kroll H, Linder M, Ruf A, Preissner KT, Chavakis T (2002) The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1. J Exp Med 196:679–691

    PubMed  CAS  Google Scholar 

  • Schenkel AR, Mamdouh Z, Chen X, Liebman RM, Muller WA (2002) CD99 plays a major role in the migration of monocytes through endothelial junctions. Nat Immunol 3:143–150

    PubMed  CAS  Google Scholar 

  • Schenkel AR, Mamdouh Z, Muller WA (2004) Locomotion of monocytes on endothelium is a critical step during extravasation. Nat Immunol 5:393–400

    PubMed  CAS  Google Scholar 

  • Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376:62–66

    PubMed  CAS  Google Scholar 

  • Shamri R, Grabovsky V, Gauguet JM, Feigelson S, Manevich E, Kolanus W, Robinson MK, Staunton DE, von Andrian UH, Alon R (2005) Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines. Nat Immunol 6:497–506

    PubMed  CAS  Google Scholar 

  • Shi GP, Sukhova GK, Kuzuya M, Ye Q, Du J, Zhang Y, Pan JH, Lu ML, Cheng XW, Iguchi A, Perrey S, Lee AM, Chapman HA, Libby P (2003) Deficiency of the cysteine protease cathepsin S impairs microvessel growth. Circ Res 92:493–500

    PubMed  CAS  Google Scholar 

  • Shi Q, Rafii S, Wu MH, Wijelath ES, Yu C, Ishida A, Fujita Y, Kothari S, Mohle R, Sauvage LR, Moore MA, Storb RF, Hammond WP (1998) Evidence for circulating bone marrow-derived endothelial cells. Blood 92:362–367

    PubMed  CAS  Google Scholar 

  • Shimaoka M, Xiao T, Liu JH, Yang Y, Dong Y, Jun CD, McCormack A, Zhang R, Joachimiak A, Takagi J, Wang JH, Springer TA (2003) Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation. Cell 112:99–111

    PubMed  CAS  Google Scholar 

  • Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, Sasaki K, Shimada T, Oike Y, Imaizumi T (2001) Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 103:2776–2779

    PubMed  CAS  Google Scholar 

  • Spring H, Schüler T, Arnold B, Hammerling GJ, Ganss R (2005) Chemokines direct endothelial progenitors into tumor neovessels. Proc Natl Acad Sci USA 102:18111–18116

    PubMed  CAS  Google Scholar 

  • Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76:301–314

    PubMed  CAS  Google Scholar 

  • Strieter RM, Burdick MD, Gomperts BN, Belperio JA, Keane MP (2005) CXC chemokines in angiogenesis. Cytokine Growth Factor Rev 16:593–609

    PubMed  CAS  Google Scholar 

  • Stypmann J, Glaser K, Roth W, Tobin DJ, Petermann I, Matthias R, Monnig G, Haverkamp W, Breithardt G, Schmahl W, Peters C, Reinheckel T (2002) Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L. Proc Natl Acad Sci USA 99:6234–6239

    PubMed  CAS  Google Scholar 

  • Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T (1999) Ischemia and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5:434–438

    PubMed  CAS  Google Scholar 

  • Tamura M, Unno K, Yonezawa S, Hattori K, Nakashima E, Tsukada H, Nakajima M, Oku N (2004) In vivo trafficking of endothelial progenitor cells their possible involvement in the tumor neovascularization. Life Sci 75:575–584

    PubMed  CAS  Google Scholar 

  • Tepel C, Bromme D, Herzog V, Brix K (2000) Cathepsin K in thyroid epithelial cells: sequence, localization and possible function in extracellular proteolysis of thyroglobulin. J Cell Sci 113:4487–4498

    PubMed  CAS  Google Scholar 

  • Tobin DJ, Foitzik K, Reinheckel T, Mecklenburg L, Botchkarev VA, Peters C, Paus R (2002) The lysosomal protease cathepsin L is an important regulator of keratinocyte and melanocyte differentiation during hair follicle morphogenesis and cycling. Am J Pathol 160:1807–1821

    PubMed  CAS  Google Scholar 

  • Urbich C, Dimmeier S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95:343–353

    PubMed  CAS  Google Scholar 

  • Urbich C, Aicher A, Heeschen C, Dernbach E, Hofmann WK, Zeiher AM, Dimmeler S (2005a) Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol 39:733–742

    PubMed  CAS  Google Scholar 

  • Urbich C, Heeschen C, Aicher A, Sasaki K, Bruhl T, Farhadi MR, Vajkoczy P, Hofmann WK, Peters C, Pennacchio LA, Abolmaali ND, Chavakis E, Reinheckel T, Zeiher AM, Dimmeler S (2005b) Cathepsin L is required for endothelial progenitor cell-induced neovascularization. Nat Med 11:206–213

    PubMed  CAS  Google Scholar 

  • Vajkoczy P, Blum S, Lamparter M, Mailhammer R, Erber R, Engelhardt B, Vestweber D, Hatzopoulos AK (2003) Multistep nature of microvascular recruitment of ex vivoexpanded embryonic endothelial progenitor cells during tumor angiogenesis. J Exp Med 197:1755–1765

    PubMed  CAS  Google Scholar 

  • Van Hinsbergh VW, Engelse MA, Quax PH (2006) Pericellular proteases in angiogenesis and vasculogenesis. Arterioscler Thromb Vasc Biol 26:716–728

    PubMed  Google Scholar 

  • Walter DH, Rittig K, Bahlmann FH, Kirchmair R, Silver M, Murayama T, Nishimura H, Losordo DW, Asahara T, Isner JM (2002) Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation 105:3017–3024

    PubMed  CAS  Google Scholar 

  • Walter DH, Haendeler J, Reinhold J, Rochwalsky U, Seeger F, Honold J, Hoffmann J, Urbich C, Lehmann R, Arenzana Seisdesdos F, Aicher A, Heeschen C, Fichtischerer S, Zeiher AM, Dimmeler S (2005) Impaired CXCR4 signaling contributes to the reduced neovascularization capacity of endothelial progenitor cells from patients with coronary artery disease. Circ Res 97:1142–1151

    PubMed  CAS  Google Scholar 

  • Werner N, Priller J, Laufs U, Endres M, Bohm M, Dirnagl U, Nickenig G (2002) Bone marrow-derived progenitor cells modulate vascular reendothelialization and neointimal formation: effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition. Arterioscler Thromb Vasc Biol 22:1567–1572

    PubMed  CAS  Google Scholar 

  • Werr J, Xie X, Hedqvist P, Ruoslahti E, Lindbom L (1998) beta1 integrins are critically involved in neutrophil locomotion in extravascular tissue In vivo. J Exp Med 187:2091–2096

    PubMed  CAS  Google Scholar 

  • Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, Chung DC, Sahani DV, Kalva SP, Kozin SV, Mino M, Cohen KS, Scadden DT, Hartford AC, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Chen HX, Shellito PC, Lauwers GY, Jain RK (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10:145–147. Epub 2004 Jan 2025

    Google Scholar 

  • Wright DE, Bowman EP, Wagers AJ, Butcher EC, Weissman IL (2002) Hematopoietic stem cells are uniquely selective in their migratory response to chemokines. J Exp Med 195:1145–1154

    CAS  Google Scholar 

  • Yamaguchi J, Kusano KF, Masuo O, Kawamoto A, Silver M, Murasawa S, Bosch-Marce M, Masuda H, Losordo DW, Isner JM, Asahara T (2003) Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemie neovascularization. Circulation 107:1322–1328

    PubMed  CAS  Google Scholar 

  • Zippo A, De Robertis A, Bardelli M, Galvagni F, Oliviero S (2004) Identification of Flk-1-target genes in vasculogenesis: Pim-1 is required for endothelial and mural cell differentiation in vitro. Blood 24:24

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular Cardiology, University of Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany

    Dr. Carmen Urbich, Emmanouil Chavakis & Stefanie Dimmeler PhD

Authors
  1. Dr. Carmen Urbich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emmanouil Chavakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefanie Dimmeler PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Klinik für Tumorbiologie, Breisacher Str. 117, 79106, Freiburg i. Br., Germany

    Dieter Marmé PhD (Professor) (Professor)

  2. DKFZ, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Norbert Fusenig MD (Professor, former Head of Division of Carcinogenesis and Differentiation) (Professor, former Head of Division of Carcinogenesis and Differentiation)

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Urbich, C., Chavakis, E., Dimmeler, S. (2008). Homing and Differentiation of Endothelial Progenitor Cells. In: Marmé, D., Fusenig, N. (eds) Tumor Angiogenesis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-33177-3_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-33177-3_17

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-33176-6

  • Online ISBN: 978-3-540-33177-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation