Advertisement

Endothelial lineage cell as a vehicle for systemic delivery of cancer gene therapy

  • Arkadiusz Z. Dudek
    Correspondence
    Reprint requests: Arkadiusz Z. Dudek, Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, MMC 480, Minneapolis, MN 55455
    Affiliations
    Divisions of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minn
    Search for articles by this author
Published:August 06, 2010DOI:https://doi.org/10.1016/j.trsl.2010.07.003
      A major limitation of cancer gene therapy is the difficulty of delivering a therapeutic gene to distant sites of metastatic disease. A promising strategy to address this difficulty is to use expanded ex vivo cells to produce a therapeutic protein. As with other approaches to gene therapy, this strategy is attractive when the therapeutic protein is unstable ex vivo or has a short circulating half life in vivo. The initial step to develop a cancer gene therapy using autologous cell delivery is the identification of a cell type that migrates to the tumor site, is readily available for harvesting, and is manipulated easily ex vivo. Recent evidence suggests that endothelial progenitor, precursor, and blood outgrowth endothelial cells are attracted to the tumor vasculature by its angiogenic drive. Here, we review recent advances in the study of circulating endothelial cell-mediated tumor vasculogenesis and discuss the advantages and challenges of bringing endothelial lineage-based cancer gene therapy closer to clinical application.

      Abbreviations:

      bFGF (basic fibroblast growth factor), BOEC (blood outgrowth endothelial cell), EBOEC (endostatin blood outgrowth endothelial cell), EC (endothelial cell), EGF (epidermal growth factor), ELC (endothelial lineage cell), EPC (endothelial cell progenitor), Flk-1 (fetal liver kinase-1), HUVEC (human umbilical vein endothelial cell), IGF (insulin-like growth factor), IGFR (IGF receptor), PBS (phosphate buffer solution), SCID (severe combined immunodeficiency), VEGF (vascular endothelial growth factor)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Roth J.C.
        • Curiel D.T.
        • Pereboeva L.
        Cell vehicle targeting strategies.
        Gene Ther. 2008; 15: 716-729
        • Purhonen S.
        • Palm J.
        • Rossi D.
        • et al.
        Bone marrow-derived circulating endothelial precursors do not contribute to vascular endothelium and are not needed for tumor growth.
        Proc Natl Acad Sci U S A. 2008; 105: 6620-6625
        • Muta M.
        • Matsumoto G.
        • Hiruma K.
        • Saji S.
        • Nakashima E.
        • Toi M.
        Impact of vasculogenesis on solid tumor growth in a rat model.
        Oncol Rep. 2003; 10: 1213-1218
        • Reyes M.
        • Dudek A.
        • Jahagirdar B.
        • Koodie L.
        • Marker P.H.
        • Verfaillie C.M.
        Origin of endothelial progenitors in human postnatal bone marrow.
        J Clin Invest. 2002; 109: 337-346
        • Timmermans F.
        • Plum J.
        • Yoder M.C.
        • Ingram D.A.
        • Vandekerckhove B.
        • Case J.
        Endothelial progenitor cells: identity defined?.
        J Cell Mol Med. 2009; 13: 87-102
        • Wei J.
        • Blum S.
        • Unger M.
        • et al.
        Embryonic endothelial progenitor cells armed with a suicide gene target hypoxic lung metastases after intravenous delivery.
        Cancer Cell. 2004; 5: 477-488
        • Kaufman D.S.
        • Lewis R.L.
        • Hanson E.T.
        • Auerbach R.
        • Plendl J.
        • Thomson J.A.
        Functional endothelial cells derived from rhesus monkey embryonic stem cells.
        Blood. 2004; 103: 1325-1332
        • Woll P.S.
        • Morris J.K.
        • Painschab M.S.
        • et al.
        Wnt signaling promotes hematoendothelial cell development from human embryonic stem cells.
        Blood. 2008; 111: 122-131
        • Xiao Q.
        • Zeng L.
        • Zhang Z.
        • et al.
        Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury.
        Arterioscler Thromb Vasc Biol. 2006; 26: 2244-2251
        • Chen T.
        • Bai H.
        • Shao Y.
        • et al.
        Stromal cell-derived factor-1/CXCR4 signaling modifies the capillary-like organization of human embryonic stem cell-derived endothelium in vitro.
        Stem Cells. 2007; 25: 392-401
        • Boyd N.L.
        • Robbins K.R.
        • Dhara S.K.
        • West F.D.
        • Stice S.L.
        Human embryonic stem cell-derived mesoderm-like epithelium transitions to mesenchymal progenitor cells.
        Tissue Eng Part A. 2009; 15: 1897-1907
        • Levenberg S.
        • Zoldan J.
        • Basevitch Y.
        • Langer R.
        Endothelial potential of human embryonic stem cells.
        Blood. 2007; 110: 806-814
        • Werbowetski-Ogilvie T.E.
        • Bosse M.
        • Stewart M.
        • et al.
        Characterization of human embryonic stem cells with features of neoplastic progression.
        Nat Biotechnol. 2009; 27: 91-97
        • Cherqui S.
        • Kurian S.M.
        • Schussler O.
        • Hewel J.A.
        • Yates 3rd, J.R.
        • Salomon D.R.
        Isolation and angiogenesis by endothelial progenitors in the fetal liver.
        Stem Cells. 2006; 24: 44-54
        • Aoki M.
        • Yasutake M.
        • Murohara T.
        Derivation of functional endothelial progenitor cells from human umbilical cord blood mononuclear cells isolated by a novel cell filtration device.
        Stem Cells. 2004; 22: 994-1002
        • Eggermann J.
        • Kliche S.
        • Jarmy G.
        • et al.
        Endothelial progenitor cell culture and differentiation in vitro: a methodological comparison using human umbilical cord blood.
        Cardiovasc Res. 2003; 58: 478-486
        • Muta M.
        • Matsumoto G.
        • Hiruma K.
        • Nakashima E.
        • Toi M.
        Study of cancer gene therapy using IL-12-secreting endothelial progenitor cells in a rat solid tumor model.
        Oncol Rep. 2003; 10: 1765-1769
        • Griese D.P.
        • Achatz S.
        • Batzlsperger C.A.
        • et al.
        Vascular gene delivery of anticoagulants by transplantation of retrovirally-transduced endothelial progenitor cells.
        Cardiovasc Res. 2003; 58: 469-477
        • Taura D.
        • Sone M.
        • Homma K.
        • et al.
        Induction and isolation of vascular cells from human induced pluripotent stem cells–brief report.
        Arterioscler Thromb Vasc Biol. 2009; 29: 1100-1103
        • Choi K.D.
        • Yu J.
        • Smuga-Otto K.
        • et al.
        Hematopoietic and endothelial differentiation of human induced pluripotent stem cells.
        Stem Cells. 2009; 27: 559-567
        • Dudek A.Z.
        • Bodempudi V.
        • Welsh B.W.
        • et al.
        Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy.
        Br J Cancer. 2007; 97: 513-522
        • van Beem R.T.
        • Verloop R.E.
        • Kleijer M.
        • et al.
        Blood outgrowth endothelial cells from cord blood and peripheral blood: angiogenesis-related characteristics in vitro.
        J Thromb Haemost. 2009; 7: 217-226
        • Jiang A.
        • Pan W.
        • Milbauer L.C.
        • Shyr Y.
        • Hebbel R.P.
        A practical question based on cross-platform microarray data normalization: are BOEC more like large vessel or microvascular endothelial cells or neither of them?.
        J Bioinform Comput Biol. 2007; 5: 875-893
        • Lin Y.
        • Chang L.
        • Solovey A.
        • Healey J.F.
        • Lollar P.
        • Hebbel R.P.
        Use of blood outgrowth endothelial cells for gene therapy for hemophilia A.
        Blood. 2002; 99: 457-462
        • Asahara T.
        • Murohara T.
        • Sullivan A.
        • et al.
        Isolation of putative progenitor endothelial cells for angiogenesis.
        Science. 1997; 275: 964-967
        • Ria R.
        • Piccoli C.
        • Cirulli T.
        • et al.
        Endothelial differentiation of hematopoietic stem and progenitor cells from patients with multiple myeloma.
        Clin Cancer Res. 2008; 14: 1678-1685
        • Li H.
        • Gerald W.L.
        • Benezra R.
        Utilization of bone marrow-derived endothelial cell precursors in spontaneous prostate tumors varies with tumor grade.
        Cancer Res. 2004; 64: 6137-6143
        • Le Ricousse-Roussanne S.
        • Barateau V.
        • Contreres J.O.
        • Boval B.
        • Kraus-Berthier L.
        • Tobelem G.
        Ex vivo differentiated endothelial and smooth muscle cells from human cord blood progenitors home to the angiogenic tumor vasculature.
        Cardiovasc Res. 2004; 62: 176-184
        • 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: 1194-1201
        • Davidoff A.M.
        • Ng C.Y.
        • 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: 2870-2879
        • Kerbel R.S.
        • Benezra R.
        • Lyden D.C.
        • et al.
        Endothelial progenitor cells are cellular hubs essential for neoangiogenesis of certain aggressive adenocarcinomas and metastatic transition but not adenomas.
        Proc Natl Acad Sci U S A. 2008; 105: E54
        • Rajantie I.
        • Ilmonen M.
        • Alminaite A.
        • Ozerdem U.
        • Alitalo K.
        • Salven P.
        Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells.
        Blood. 2004; 104: 2084-2086
        • Gao D.
        • Nolan D.J.
        • Mellick A.S.
        • Bambino K.
        • McDonnell K.
        • Mittal V.
        Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis.
        Science. 2008; 319: 195-198
        • Liao D.
        • Johnson R.S.
        Hypoxia: a key regulator of angiogenesis in cancer.
        Cancer Metastasis Rev. 2007; 26: 281-290
        • Moore X.L.
        • Lu J.
        • Sun L.
        • Zhu C.J.
        • Tan P.
        • Wong M.C.
        Endothelial progenitor cells’ “homing” specificity to brain tumors.
        Gene Ther. 2004; 11: 811-818
        • Wei J.
        • Jarmy G.
        • Genuneit J.
        • Debatin K.M.
        • Beltinger C.
        Human blood late outgrowth endothelial cells for gene therapy of cancer: determinants of efficacy.
        Gene Ther. 2007; 14: 344-356
        • Jevremovic D.
        • Gulati R.
        • Hennig I.
        • et al.
        Use of blood outgrowth endothelial cells as virus-producing vectors for gene delivery to tumors.
        Am J Physiol Heart Circ Physiol. 2004; 287: H494-H500
        • Wei J.
        • Zhou S.
        • Bachem M.G.
        • Debatin K.M.
        • Beltinger C.
        Infiltration of blood outgrowth endothelial cells into tumor spheroids: role of matrix metalloproteinases and irradiation.
        Anticancer Res. 2007; 27: 1415-1421
        • Griffin R.J.
        • Williams B.W.
        • Wild R.
        • Cherrington J.M.
        • Park H.
        • Song C.W.
        Simultaneous inhibition of the receptor kinase activity of vascular endothelial, fibroblast, and platelet-derived growth factors suppresses tumor growth and enhances tumor radiation response.
        Cancer Res. 2002; 62: 1702-1706
        • Spring H.
        • Schuler T.
        • Arnold B.
        • Hammerling G.J.
        • Ganss R.
        Chemokines direct endothelial progenitors into tumor neovessels.
        Proc Natl Acad Sci U S A. 2005; 102: 18111-18116
        • Maeng Y.S.
        • Choi H.J.
        • Kwon J.Y.
        • et al.
        Endothelial progenitor cell homing: prominent role of the IGF2-IGF2R-PLCbeta2 axis.
        Blood. 2009; 113: 233-243
        • Modlich U.
        • Pugh C.W.
        • Bicknell R.
        Increasing endothelial cell specific expression by the use of heterologous hypoxic and cytokine-inducible enhancers.
        Gene Ther. 2000; 7: 896-902
        • Binley K.
        • Askham Z.
        • Martin L.
        • et al.
        Hypoxia-mediated tumour targeting.
        Gene Ther. 2003; 10: 540-549
        • Varda-Bloom N.
        • Shaish A.
        • Gonen A.
        • et al.
        Tissue-specific gene therapy directed to tumor angiogenesis.
        Gene Ther. 2001; 8: 819-827
        • Yang L.
        • Cao Z.
        • Li F.
        • et al.
        Tumor-specific gene expression using the survivin promoter is further increased by hypoxia.
        Gene Ther. 2004; 11: 1215-1223
        • Shaked Y.
        • Kerbel R.S.
        Antiangiogenic strategies on defense: on the possibility of blocking rebounds by the tumor vasculature after chemotherapy.
        Cancer Res. 2007; 67: 7055-7058
        • Sonveaux P.
        • Brouet A.
        • Havaux X.
        • et al.
        Irradiation-induced angiogenesis through the up-regulation of the nitric oxide pathway: implications for tumor radiotherapy.
        Cancer Res. 2003; 63: 1012-1019
        • Cai H.
        • Gehrig P.
        • Scott T.M.
        • Zimmermann R.
        • Schlapbach R.
        • Zisch A.H.
        MnSOD marks cord blood late outgrowth endothelial cells and accompanies robust resistance to oxidative stress.
        Biochem Biophys Res Commun. 2006; 350: 364-369
        • Kealy B.
        • Liew A.
        • McMahon J.M.
        • et al.
        Comparison of viral and nonviral vectors for gene transfer to human endothelial progenitor cells.
        Tissue Eng Part C Methods. 2009; 15: 223-231
        • Tran J.
        • Master Z.
        • Yu J.L.
        • Rak J.
        • Dumont D.J.
        • Kerbel R.S.
        A role for survivin in chemoresistance of endothelial cells mediated by VEGF.
        Proc Natl Acad Sci U S A. 2002; 99: 4349-4354
        • Freeman S.M.
        • Abboud C.N.
        • Whartenby K.A.
        • et al.
        The “bystander effect”: tumor regression when a fraction of the tumor mass is genetically modified.
        Cancer Res. 1993; 53: 5274-5283
        • Rancourt C.
        • Robertson 3rd, M.W.
        • Wang M.
        • et al.
        Endothelial cell vehicles for delivery of cytotoxic genes as a gene therapy approach for carcinoma of the ovary.
        Clin Cancer Res. 1998; 4: 265-270
        • Arafat W.O.
        • Casado E.
        • Wang M.
        • et al.
        Genetically modified CD34+ cells exert a cytotoxic bystander effect on human endothelial and cancer cells.
        Clin Cancer Res. 2000; 6: 4442-4448
        • De Palma M.
        • Venneri M.A.
        • Roca C.
        • Naldini L.
        Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells.
        Nat Med. 2003; 9: 789-795
        • Ferrari N.
        • Glod J.
        • Lee J.
        • Kobiler D.
        • Fine H.A.
        Bone marrow-derived, endothelial progenitor-like cells as angiogenesis-selective gene-targeting vectors.
        Gene Ther. 2003; 10: 647-656
        • Benouchan M.
        • Do Nascimento F.
        • Perret G.Y.
        • Colombo B.M.
        Delivery of the bacterial nitroreductase gene into endothelial cells prolongs the survival of tumour-bearing mice by bystander mechanisms.
        Int J Oncol. 2006; 28: 457-462
        • Wei J.
        • Wahl J.
        • Nakamura T.
        • et al.
        Targeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas.
        Gene Ther. 2007; 14: 1573-1586
        • Somani A.
        • Nguyen J.
        • Milbauer L.C.
        • Solovey A.
        • Sajja S.
        • Hebbel R.P.
        The establishment of murine blood outgrowth endothelial cells and observations relevant to gene therapy.
        Transl Res. 2007; 150: 30-39
        • Ojeifo J.O.
        • Lee H.R.
        • Rezza P.
        • Su N.
        • Zwiebel J.A.
        Endothelial cell-based systemic gene therapy of metastatic melanoma.
        Cancer Gene Ther. 2001; 8: 636-648