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Tumor Angiogenesis: from Bench to Bedside

  • Chapter
Tumor Angiogenesis

Abstract

An association between cancer and blood vessels has been observed for more than a century. These reports dealt mainly with angioarchitecture of tumors, vascular patterns unique to tumors, effects of irradiation on tumor vasculature, alteration in tumor blood flow, increased vascularity of the peripheral shell of tumors, and the delivery of intravital dyes and anti-cancer drugs to the tumor bed (Thiersch 1865; Goldmann 1907; Thiessen 1936). In a few reports, experimental tumors were transplanted into transparent chambers in the mouse or rabbit. In some reports, the tumor and the host vascular bed were separated by a micropore filter to determine whether a diffusible substance was released from tumors that could stimulate blood vessel growth (Ide et al. 1939; Algire 1943; Algire and Legallais 1947; Toolan 1951; Greene 1952; Day et al. 1959; Zweifach 1961; Gullino and Grantham 1962; Goldacre and Sylvén 1962; Warner 1964; Greenblatt and Shubik 1968; Greenblatt et al 1969; Rubin and Casarett 1966; Tannock 1970).For a definitive historical review from 1865 to 1970, (see (1979)). Furthermore, surgeons often reported excessive bleeding from tumors, and “serpentiginous veins” on the surface of tumors. Numerous explanations for these findings were offered in the literature. The vascularity of tumors was attributed to vasodilation, inf lammation, dying tumor cells, increased tumor metabolism, overproduction of lactic acid or uric acid, or hypoxia from “tumors outgrowing their blood supply.” There were no molecular mediators of angiogenesis in these reports. One of the most common assumptions prior to 1970 was that excessive vascularity of tumors was a side effect of growing tumors or dying tumor cells.

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References

  • Abdollahi A, Hahnfeldt P, Maercker C, Gröne HJ, Debus J, Ansorge W, Folkman J, Hlatky L, Huber PE (2004) Endostatin’s antiangiogenic signaling network. Molecular Cell 13:649–663

    PubMed  CAS  Google Scholar 

  • Achilles E-G, Fernandez A, Allred EN, Kisker O, Udagawa T, Beecken W-D, Flynn E, Folkman J (2001) Heterogeneity of angiogenic activity in a human liposarcoma: A proposed mechanism for ‘no take’ of human tumors in mice. J Natl Cancer Inst 93:1075–1081

    PubMed  CAS  Google Scholar 

  • Adamis, AP, Shima DT, Yeo K-T, Yeo T-K, Brown LF, Berse B, D’Amore PA, Folkman J (1993) Synthesis and secretion of vascular permeability factor/vascular endothelial growth factor by human retinal pigment epithelial cells. Biochem Biophys Res Commun 193:631–638

    PubMed  CAS  Google Scholar 

  • Adamis AP, Miller JW, Bernai M-T, D’Amico DJ, Folkman J, Yeo T-K, Yeo K-T (1994) Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthal 118(4):445–450

    PubMed  CAS  Google Scholar 

  • Adamis AP, Shima DT, Tolentino MJ, Gragoudas ES, Ferrara N, Folkman J, D’Amore PA, Miller JW (1996) Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. Arch Ophthalmol 114:66–71

    PubMed  CAS  Google Scholar 

  • Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, Nguyen HV, Aiello LM, Ferrara N, King GA (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487

    PubMed  CAS  Google Scholar 

  • Algire GH (1943) Microscopic studies of the early growth of a transplantable melanoma of the mouse, using the transparent chamber technique. J Natl Cancer Inst 4:1

    Google Scholar 

  • Algire GH, Legallais FY (1947) Growth rate of transplantable tumor in relation to latent period and host vascular reaction. Cancer Res 7:724

    Google Scholar 

  • Almog N, Henke V, Flores L, Hlatky L, Kung AL, Wright RD, Berger R, Hutchinson L, Naumov GN, Bender E, Akslen LA, Achilles EG, Folkman J (2006) Prolonged dormancy of human liposarcoma is associated with impaired tumor angiogenesis. FASEB J 20:947–949

    PubMed  CAS  Google Scholar 

  • Ambati BK, Nozaki M, Singh N, Takeda A, Jani PD, Suthar T, Albuquerque RJ, Richter E, Sakurai E, Newcomb MT, Kleinman ME, Caldwell RB, Lin Q, Ogura Y, Orecchia A, Samuelson DA, Agnew DW, St Leger J, Green WR, Mahasreshti PJ, Curiel DT, Kwan D, Marsh H, Ikeda S, Leiper LJ, Collinson JM, Bogdanovich S, Khurana TS, Shibuya M, Baldwin ME, Ferrara N, Gerber HP, De Falco S, Witta J, Baffi JZ, Raisler BJ, Ambati J (2006) Corneal avascularity is due to soluble VEGF receptor-1. Nature 443:993–997

    PubMed  CAS  Google Scholar 

  • Arbiser JL, Moses MA, Fernandez CA, Ghiso N, Cao Y, Klauber N, Frank D, Brownlee M, Flynn E, Parangi S, Byers HR, Folkman J (1997) Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways. Proc Natl Acad Sci USA 94:861–866

    PubMed  CAS  Google Scholar 

  • Auerbach W, Auerbach R (1994) Angiogenesis inhibition: a review. Pharmacol Therap 63:265–311

    CAS  Google Scholar 

  • Auerbach R, Kubai L, Knighton D, Folkman J (1974) A simple procedure for the long-term cultivation of chicken embryo. Dev Biol 41:391–394

    PubMed  CAS  Google Scholar 

  • Ausprunk DH, Folkman J (1977) Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 14:53–65

    PubMed  CAS  Google Scholar 

  • Ausprunk DH, Knighton DR, Folkman J (1974) Differentiation of vascular endothelium in the chick chorioallantois: a structural and autoradiographic study. Dev Biol 38:237–248

    PubMed  CAS  Google Scholar 

  • Ausprunk DH, Knighton DR, Folkman J (1975) Vascularization of normal and neoplastic tissues grafted to the chick chorioallantois. Am J Pathol 79(3):597–610

    PubMed  CAS  Google Scholar 

  • Ausprunk DH, Falterman K, Folkman J (1978) The sequence of events in the regression of corneal capillaries. Lab Invest 38:284–294

    PubMed  CAS  Google Scholar 

  • Bashkin P, Doctrow S, Klagsbrun M, Svahn CM, Folkman J, Vlodavsky I (1989) Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules. Biochem 28:1737–1743

    CAS  Google Scholar 

  • Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, Ancukiewicz M, Mrugala MM, Plotkin S, Drappatz J, Louis DN, Ivy P, Scadden DT, Benner T, Loeffler JS, Wen PY, Jain RK (2007) AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11:83–95

    PubMed  CAS  Google Scholar 

  • Bissell MJ, Farson D, Tung AS (1977) Cell shape and hexose transport in normal and virus-transformed cells in culture. J Supramolecular Structure 6:1–12

    CAS  Google Scholar 

  • Boehm T, Folkman J, Browder T, O’Reilly MS (1997) Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390 404–407

    PubMed  CAS  Google Scholar 

  • Brem H, Arensman R, Folkman J (1975) Inhibition of tumor angiogenesis by a diffusible factor from cartilage. In: Slavkin HC, Greulich RC (eds) Extracellular matrix influences on gene expression. Academic Press, New York, pp 767–772

    Google Scholar 

  • Brouty-Boye D, Zetter B (1980) Inhibition of cell motility by interferon. Science 208:516–518

    PubMed  CAS  Google Scholar 

  • Browder T, Butterfield CE, Kräling BM, Shi B, Marshall B, O’Reilly MS, Folkman J (2000) Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 60:1878–1886

    PubMed  CAS  Google Scholar 

  • Brown LR, Wei CL, Langer R (1983) In vivo and in vitro release of macromolecules from drug delivery systems. J Pharm Sci 72:1181–1185

    PubMed  CAS  Google Scholar 

  • Cao Y, O’Reilly MS, Marshall B, Flynn E, Ji RW, Folkman J (1998) Expression of angiostatin cDNA in a murine fibrosarcoma suppresses primary tumor growth and produces long-term dormancy of metastases. J Clin Invest 101:1055–1063

    PubMed  CAS  Google Scholar 

  • Camphausen K, Moses MA, Beecken WD, Khan MK, Folkman J, O’Reilly MS (2001) Radiation therapy to a primary tumor accelerates metastatic growth in mice. Cancer Res 61:2207–2211

    PubMed  CAS  Google Scholar 

  • Carmeliet P, Jain R (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257

    PubMed  CAS  Google Scholar 

  • Casanovas O, Hicklin DJ, Bergers G, Hanahan D (2005) Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8:299–309

    PubMed  CAS  Google Scholar 

  • Cavallo T, Sade R, Folkman J, Cotran RS (1972) Tumor angiogenesis: rapid induction of endothelial mitoses demonstrated by autoradiography. J Cell Biol 54:408–420

    PubMed  CAS  Google Scholar 

  • Celik I, Surucu O, Dietz C, Heymach JV, Force J, Hoschele I, Becker CM, Folkman J, Kisker O (2005) Therapeutic efficacy of endostatin exhibits a biphasic dose-response curve. Cancer Res 65:11044–11050

    PubMed  CAS  Google Scholar 

  • Chang LK, Garcia-Cardena G, Farnebo F, Fannon M, Chen EJ, Butterfield C, Moses MA, Mulligan RC, Folkman J, Kaipainen A (2004) Dose-dependent response of FGF-2 for lymphangiogenesis. Proc Natl Acad Sci USA 101:11658–11663

    PubMed  CAS  Google Scholar 

  • Chen NT, Corey EJ, Folkman J (1988) Potentiation of angiostatic steroids by a synthetic inhibitor of arylsulfatase. Lab Invest 59:453–459

    PubMed  CAS  Google Scholar 

  • Chin L, Tarn A, Pomerantz J, Wong M, Holash J, Bardeesy N, Shen Q, O’Hagan R, Pantginis J, Zhou H, Horner JW, Cordon-Cardo C, Yancopoulos GD, DePinho RA (1999) Essential role for oncogenic Ras in tumour maintenance. Nature 400:468–472

    PubMed  CAS  Google Scholar 

  • Crum R, Szabo S, Folkman J (1985) A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 230:1375–1378

    PubMed  CAS  Google Scholar 

  • Dameron KM, Volpert OM, Tainsky MA, Bouck N (1994) Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science 265:1582–1584

    PubMed  CAS  Google Scholar 

  • D’Amato RJ, Lin CM, Flynn E, Folkman J, Hamel E (1994) 2-Methoxyestradiol, an endogenous mammalian metabolite, inhibits tubulin polymerization by interacting at the colchicine site. Proc Natl Acad Sci USA 91:3964–3968

    PubMed  CAS  Google Scholar 

  • Day ED, Planinsek JA, Pressman D (1959) Localization of radio iodinated rat fibrinogen in transplanted rat tumors. J Natl Cancer Inst 23:799

    PubMed  CAS  Google Scholar 

  • Dvorak HF, Gresser I (1989) Microvascular injury in pathogenesis of interferon-induced necrosis of subcutaneous tumors in mice. J Natl Cancer Inst 81:497–502

    PubMed  CAS  Google Scholar 

  • Ehrmann RL, Knoth M (1968) Choriocarcinoma. Transfilter stimulation of vasoproliferation in the hamster cheek pouch. Studied by light and electron microscopy. J Natl Cancer Inst 41:1329–1341

    PubMed  CAS  Google Scholar 

  • Esch F, Esch F, Baird A, Ling N, Ueno N, Hill F, Denoroy L, Klepper R, Gospodarowicz D, Bohlen P, Guillemin R (1985) Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc Natl Acad Sci USA 82:6507–6511

    PubMed  CAS  Google Scholar 

  • Ezzell C (1998) Starving tumors of their lifeblood. Sci Am 279:33–34

    PubMed  CAS  Google Scholar 

  • Ferrara N, Henzel WJ (1989) Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161:851–858

    PubMed  CAS  Google Scholar 

  • Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    PubMed  CAS  Google Scholar 

  • Folkman J (1974a) Tumor angiogenesis. In Klein G, Weinhouse S (eds) Advances in cancer research, vol 19. Academic Press, New York, pp 19:331–358

    Google Scholar 

  • Folkman J (1974b) Tumor angiogenesis: role in regulation of tumor growth. In: Hay, ED, King TJ, Papaconstantinou J (eds) Macromolecules regulating growth and development. Academic Press, New York, pp 43–52

    Google Scholar 

  • Folkman J (1975) Tumor angiogenesis. In: Becker FF (ed) Cancer: comprehensive treatise. Plenum Press, New York, pp 3:355–388

    Google Scholar 

  • Folkman J (1978) Tumor angiogenesis and tumor immunity. In: Castro JE (ed) Immunological aspects of cancer. MTP Press, Lancaster, pp 267–282

    Google Scholar 

  • Folkman J (1989) Successful treatment of an angiogenic disease. N Engl J Med 320:1211–1212

    PubMed  CAS  Google Scholar 

  • Folkman J (2002) Discussion. Antiangiogenic therapy with interferon alpha for giant cell lesions of the jaws. J Oral Maxillofac Surg 60:1111–1113

    Google Scholar 

  • Folkman J (2004) Endogenous angiogenesis inhibitors. Acta Pathol Microbiol Immunol Scand 112:496–507

    CAS  Google Scholar 

  • Folkman J (2006) Antiangiogenesis in cancer therapy endostatin and its mechanisms of action. Exp Cell Res 312:594–607

    PubMed  CAS  Google Scholar 

  • Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nature Reviews Drug Discovery 6:273–286

    PubMed  CAS  Google Scholar 

  • Folkman J, Cotran RS (1976) Relation of vascular proliferation to tumor growth. In: Richter GW (ed) International review of experimental pathology. Academic Press, New York, pp 16:207–248

    Google Scholar 

  • Folkman J, Gimbrone MA Jr (1971) Perfusion of the thyroid. In: Diczfalusy E (ed) Karolinska Symposia on Research Methods in Reproduction Endocrinology, 4th Symposium: Perfusion Techniques. Stockholm: Karolinska Institutet 4:237–248

    Google Scholar 

  • Folkman J, Gimbrone MA Jr (1975) Perfusion of the thyroid gland. In: Hardman JG, O’Malley BW (eds) Methods in enzymology. Hormone action, part D. Isolated cells, tissues and organ systems. Academic Press, New York, pp 39:359–364

    Google Scholar 

  • Folkman J, Haudenschild C (1980) Angiogenesis in vitro. Nature 288:551–556

    PubMed  CAS  Google Scholar 

  • Folkman J, Klagsbrun M (1975) Tumor angiogenesis: effect on tumor growth and immunity. In: Gottlieb AA, Plescia OJ, Bishop DHL (eds) Fundamental aspects of neoplasia. Springer, New York, pp 401–412

    Google Scholar 

  • Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442–447

    PubMed  CAS  Google Scholar 

  • Folkman J, Long DM (1964) The use of silicone rubber as a carrier for prolonged drug therapy. J Surg Res 4:139–142

    PubMed  CAS  Google Scholar 

  • Folkman J, Moscona A (1978) Role of cell shape in growth control. Nature 273:345–349

    PubMed  CAS  Google Scholar 

  • Folkman J, Ryeom S (2005) Is oncogene addiction angiogenesis-dependent? Cold Spring Harb Symp Quant Biol 70:389–397

    PubMed  CAS  Google Scholar 

  • Folkman MJ, Long DM, Becker FF (1962) Tumor growth in organ culture. Surg Forum 13:164–166

    Google Scholar 

  • Folkman J, Long DM, Becker FF (1963) Growth and metastasis of tumor in organ culture. Cancer 16:453–467

    PubMed  CAS  Google Scholar 

  • Folkman J, Cole P, Zimmerman S (1966) Tumor behavior in isolated perfused organs: in vitro growth and metastases of biopsy material in rabbit thyroid and canine intestinal segment. Ann Surg 164:491–502

    PubMed  CAS  Google Scholar 

  • Folkman J, Hochberg M, Knighton D (1974) Self-regulation of growth in three dimensions: the role of surface area limitation. In: Clarkson B, Baserga R (eds) Cold Spring Harbor Symposium. Control of proliferation in animal cells. Cold Spring Harbor, New York, pp 833–842

    Google Scholar 

  • Folkman J, Haudenschild CC, Zetter BR (1979) Long-term culture of capillary endothelial cells. Proc Natl Acad Sci USA 76:5217–5221

    PubMed  CAS  Google Scholar 

  • Folkman J, Klagsbrun M, Sasse J, Wadzinski M, Ingber D, Vlodavsky I (1988) A heparin-binding angiogenic protein — basic fibroblast growth factor — is stored within basement membrane. Am J Pathol 130:393–400

    PubMed  CAS  Google Scholar 

  • Folkman J, Browder T, Palmblad J (2001) Angiogenesis research: guidelines for translation to clinical application. Thromb Haemost 86:23–33

    PubMed  CAS  Google Scholar 

  • Fotsis T, Zhang Y, Pepper MS, Adlercreutz H, Montesano R, Nawroth PP, Schweigerer L (1994) The endogenous oestrogen metabolite 2-methoxyestradiol inhibits angiogenesis and suppresses tumor growth. Nature 368:237–239

    PubMed  CAS  Google Scholar 

  • Gimbrone MA Jr, Aster RH, Cotran RS, Corkery J, Jandl JH, Folkman J (1969) Preservation of vascular integrity in organs perfused in vitro with a platelet-rich medium. Nature 222:33–36

    PubMed  Google Scholar 

  • Gimbrone MA Jr, Leapman SB, Cotran RS, Folkman J (1972) Tumor dormancy in vivo by prevention of neovascularization. J Exp Med 136(2):261–276

    PubMed  Google Scholar 

  • Gimbrone MA Jr, Cotran RS, Folkman J (1973) Endothelial regeneration: studies with human endothelial cell cultures. Ser Haematol 6:453–455

    PubMed  Google Scholar 

  • Gimbrone MA Jr, Cotran RS, Leapman SB, Folkman J (1974a) Tumor growth and neovascularization: an experimental model using rabbit cornea. J Natl Canc Inst 52(2):413–427

    Google Scholar 

  • Gimbrone MA Jr, Cotran RS, Folkman J (1974b) Human vascular endothelial cells in culture: growth and DNA synthesis. J Cell Biol 60:673–684

    PubMed  CAS  Google Scholar 

  • Giuriato S, Ryeom S, Fan AC, Bachireddy P, Lynch RC, Rioth MJ, van Riggelen J, Kopelman AM, Passegue E, Tang F, Folkman J, Felsher DW (2006) Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switch. Proc Natl Acad Sci USA 103:16266–16271

    PubMed  CAS  Google Scholar 

  • Goldacre RJ, Sylvén B (1962) On the access of blood borne dyes to various tumor regions. Br J Cancer 16:306

    PubMed  CAS  Google Scholar 

  • Goldmann E (1907) Growth of malignant disease in man and the lower animals with special reference to vascular system. Proc R Soc Med 1:1

    Google Scholar 

  • Gospodarowicz D (1974) Localization of a fibroblast growth factor and its effect with hydrocortisone on 3T3 cell growth. Nature 249:123–127

    PubMed  CAS  Google Scholar 

  • Gospodarowicz D, Moran J, Braun D, Birdwell C (1976) Clonal growth of bovine endothelial cells: fibroblast growth factor as a survival agent. Proc Natl Acad Sci USA 73:4120–4124

    PubMed  CAS  Google Scholar 

  • Greene HSN (1952) The significance of the heterologous transplantability of human cancer. Cancer 5:24

    PubMed  CAS  Google Scholar 

  • Greenblatt M, Shubik P (1968) Tumor angiogenesis: transfilter diffusion studies in the hamster by the transparent chamber technique. J Natl Cancer Inst 41:111–124

    PubMed  CAS  Google Scholar 

  • Greenblatt M, Choudari KVR, Sanders AG, Shubik P (1969) Mammalian microcirculation in the living animal: microcirculation of renal homograft transplants in hamsters. Am J Pathol 56:317

    PubMed  CAS  Google Scholar 

  • Gullino PM, Grantham FH (1962) Studies on the exchange of fluids between host and tumor. III. Regulation of blood flow in hepatomas and other rat tumors. J Natl Cancer Inst 28:211

    PubMed  CAS  Google Scholar 

  • Hamano Y, Kalluri R (2005) Tumstatin, the NCI domain of alpha3 chain of type IV collagen, is an endogenous inhibitor of pathological angiogenesis and suppresses tumor growth. Biochem Biophys Res Commun 333:292–298

    PubMed  CAS  Google Scholar 

  • Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364

    PubMed  CAS  Google Scholar 

  • Hanahan D, Bergers G, Bergsland E (2000) Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 105:1045–1047

    PubMed  CAS  Google Scholar 

  • Haudenschild CC, Zahniser D, Folkman J, Klagsbrun M (1976) Human vascular endothelial cells in culture. Lack of response to serum growth factors. Exp Cell Res 98:175–183

    PubMed  CAS  Google Scholar 

  • Hellstrom M, Phng LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson AK, Karlsson L, Gaiano N, Yoon K, Rossant J, Iruela-Arispe ML, Kalen M, Gerhardt H, Betsholtz C (2007) D114 signalling through Notchl regulates formation of tip cells during angiogenesis. Nature 445:776–780

    PubMed  Google Scholar 

  • Holmgren L, O’Reilly MS, Folkman J (1995) Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1:149–153

    PubMed  CAS  Google Scholar 

  • Huang S, Ingber DE (2005) Cell tension, matrix mechanics, and cancer development. Cancer Cell 8:175–176

    PubMed  CAS  Google Scholar 

  • Ide AG, Baker NH, Warren SL (1939) Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am J Roentgenol 42:891

    Google Scholar 

  • Ingber DE, Folkman J (1989a) How does extracellular matrix control capillary morphogenesis? Cell 58:803–805

    PubMed  CAS  Google Scholar 

  • Ingber DE, Folkman J (1989b) Tension and compression as basic determinants of cell form and function: utilization of a cellular tensegrity mechanism. In: Stein W, Bronner F (eds) Cell shape: determinants, regulation, and regulatory role. Academic Press, New York, pp 3–31

    Google Scholar 

  • Ingber DE, Folkman J (1989c) Mechanochemical switching between growth and differentiation during fibroblast growth factor — stimulated angiogenesis in vitro: role of extracellular matrix. J Cell Biol 109:317–330

    PubMed  CAS  Google Scholar 

  • Ingber DE, Madri JA, Folkman J (1987) Endothelial growth factors and extracellular matrix regulate DNA synthesis through modulation of cell and nuclear expansion. In Vitro Cell Dev Biol 23:387–394

    PubMed  CAS  Google Scholar 

  • Italiano J, Richardson JL, Folkman J, Klement G (2006) Blood platelets organize pro-and anti-angiogenic factors into separate, distinct alpha granules: implications for the regulation of angiogenesis. Blood 108:120a, abstract 393

    Google Scholar 

  • Jaffe EA, Nachman RL, Becker CG, Minick CR (1973) Culture of human endothelial cells derived from umbilical veins. Ientification by morphologic and immunologie criteria. J Clin Invest 52:2745–2756

    PubMed  CAS  Google Scholar 

  • Jain RK (1988) Determinants of tumor blood flow: a review. Cancer Res 48:2641–2658

    PubMed  CAS  Google Scholar 

  • Jain RK (1994) Barriers to drug delivery. Sci Am 271:58–65

    PubMed  CAS  Google Scholar 

  • Jain RK (2001) Normalizing tumor vasculature with antiangiogenic therapy: a new paradigm for combination therapy. Nat Med 7:987–989

    PubMed  CAS  Google Scholar 

  • Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62

    PubMed  CAS  Google Scholar 

  • Jain M, Arvanitis C, Chu K, Dewey W, Leonhardt E, Trinh M, Sundberg CD, Bishop JM, Felsher DW (2002) Sustained loss of a neoplastic phenotype by brief inactivation of MYC. Science 297:102–104

    PubMed  CAS  Google Scholar 

  • Kaban LB, Mulliken JB, Ezekowitz RA, Ebb D, Smith PS, Folkman J (1999) Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon alfa-2a. Pediatrics 103:1145–1149

    PubMed  CAS  Google Scholar 

  • Kaban LB, Troulis MJ, Ebb D, August M, Hornicek FJ, Dodson TB (2002) Antiangiogenic therapy with interferon alpha for giant cell lesions of the jaws. J Oral Maxillofac Surg 60:1103–1111

    PubMed  Google Scholar 

  • Kamphaus GD, Colorado PC, Panka DJ, Hopfer H, Ramchandran R, Torre A, Maeshima Y, Mier JW, Sukhatme VP, Kalluri R (2000) Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. J Biol Chem 275:1209–1215

    PubMed  CAS  Google Scholar 

  • Kisker O, Onizuka S, Becker CM, Fannon M, Flynn E, D’Amato R, Zetter B, Folkman J, Ray R, Swamy N, Pirie-Shepherd S (2003) Vitamin D binding protein-macrophage activating factor (DBP-maf) inhibits angiogenesis and tumor growth in mice. Neoplasia 5:32–40

    PubMed  CAS  Google Scholar 

  • Klement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ, Bohlen P, Klerbel RS (2000) Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 105:R15–24

    PubMed  CAS  Google Scholar 

  • Klement G, Kikuchi L, Kieran M, Almog N, Yip TT, Folkman J (2004) Early tumor detection using platelets uptake of angiogenesis regulators. Proc 47th American Society of Hematology. Blood 104:239a, abstract 839

    Google Scholar 

  • Klement G, Cervi D, Yip T, Folkman J, Italiano J (2006) Platelet PF-4 is an early marker of tumor angiogenesis. Blood 108:426a, abstract 1476

    Google Scholar 

  • Knighton D, Ausprunk D, Tapper D, Folkman J (1977) Avascular and vascular phases of tumor growth in the chick embryo. Br J Canc 35:347–356

    CAS  Google Scholar 

  • Kuo C, LaMontagne KR Jr, Garcia-Cardena G, Ackley BD, Kaiman D, Parks S, Christofferson R, Kamihara J, Ding Y-H, Lo K-M, Gillies S, Folkman J, Mulligan RC, Javaherian K (2001) Oligomerization-dependent regulation of motility and morphogenesis by the collagen XVIII NCI/ endostatin domain. J Cell Biol 152:1233–1246

    PubMed  CAS  Google Scholar 

  • Langer R, Folkman J (1976) Polymers for the sustained release of proteins and other macromolecules. Nature 263:797–800

    PubMed  CAS  Google Scholar 

  • Lobov IB, Renard RA, Papadopoulos N, Gale NW, Thurston G, Yancopoulos GD, Wiegand SJ (2007) Delta-like ligand 4 (D114) is induced by VEGF as a negative regulator of angiogenic sprouting. Proc Natl Acad Sci USA (in press)

    Google Scholar 

  • Marier JJ, Rubin JB, Trede NS, Connors S, Grier H, Upton J, Mulliken JB, Folkman J (2002) Successful antiangiogenic therapy of giant cell angioblastoma with interferon alpha 2b: report of 2 cases. Pediatrics 109:E37

    Google Scholar 

  • Miao HQ, Lee P, Lin H, Soker S, Klagsbrun M(2000) Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression. FASEB J 14:2532–2539

    PubMed  CAS  Google Scholar 

  • Miller JW, Adamis AP, Shima DT, D’Amore PA, Moulton RS, O’Reilly MS, Folkman J, Dvorak HF, Brown LF, Berse B, Yeo T-K, Yeo K-T (1994) Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am J Pathol 145:574–584

    PubMed  CAS  Google Scholar 

  • Murray JC (2001) Angiogenesis protocols, Humana Press, Totowa, New Jersey

    Google Scholar 

  • Muthukkaruppan V, Auerbach R (1979) Angiogenesis in the mouse cornea. Science 205:1416–1418

    PubMed  CAS  Google Scholar 

  • Naumov GN, Bender E, Zurakowski D, Kang SY, Sampson D, Flynn E, Watnick RS, Straume O, Akslen LA, Folkman J, Almog N (2006a) A model of human tumor dormancy: an angiogenic switch from the nonangiogenic phenotype. J Natl Cancer Inst 98:316–325

    PubMed  Google Scholar 

  • Naumov GN, Akslen LA, Folkman J (2006b) Role of angiogenesis in human tumor dormancy. Cell Cycle 5:1779–1787

    PubMed  CAS  Google Scholar 

  • Noguera-Troise I, Daly C, Papadopoulos NJ, Coetzee S, Boland P, Gale NW, Lin HC, Yancopoulos GD, Thurston G (2006) Blockade of D114 inhibits tumour growth by promoting non-productive angiogenesis. Nature 444:1032–1037

    PubMed  CAS  Google Scholar 

  • Norrby K (2006) In vivo models of angiogenesis. J Cell Mol Med 10:588–612

    PubMed  CAS  Google Scholar 

  • Nguyen M, Watanabe H, Budson AE, Richie JP, Folkman J (1993) Elevated levels of the angiogenic peptide basic fibroblast growth factor in urine of bladder cancer patients. J Natl Cancer Inst 85:241–242

    PubMed  CAS  Google Scholar 

  • Nguyen M, Shing Y, Folkman J (1994) Quantitation of angiogenesis and antiangiogenesis in the chick embryo chorioallantoic membrane. Microvasc Res 47:31–40

    PubMed  CAS  Google Scholar 

  • Nyberg P, Xie L, Kalluri R (2005) Endogenous inhibitors of angiogenesis. Cancer Res 65:3967–3979

    PubMed  CAS  Google Scholar 

  • O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79:315–328

    PubMed  CAS  Google Scholar 

  • O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277–285

    PubMed  CAS  Google Scholar 

  • Panigrahy D, Singer S, Shen LQ, Butterfield CE, Freedman DA, Chen EJ, Moses MA, Kilroy S, Duensing S, Fletcher C, Fletcher JA, Hlatky L, Hahnfeldt P, Folkman J, Kaipainen A (2002) PPARγ ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. J Clin Invest 110:923–932

    PubMed  CAS  Google Scholar 

  • Peterson H-I (ed) (1979) Tumor blood circulation: angiogenesis, vascular morphology, and blood flow of experimental and human tumors. CRC Press, West Palm Beach, Fla

    Google Scholar 

  • Rak J; Yu JL; Klement G; Kerbel RS (2000) Oncogenes and angiogenesis: signaling three-dimensional tumor growth. J Investig Dermatol Symp Proc 5:24–33

    PubMed  CAS  Google Scholar 

  • Reif M, LeJeune S, Scott PA, Fox S, Smith K, Leek R, Moghaddam A, Whitehouse R, Bicknell R, Harris AL (1997) Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 57:963–969

    Google Scholar 

  • Ribatti D, Locci P, Marinucci L, Lilli C, Roncali L, Becchetti E (1995). Exogenous heparin induces an increase in glycosaminoglycans of the chick embryo chorioallantoic membrane: its possible role in the regulation of angiogenic processes. Int J Microcirculation Clin Exp 15:181–185

    CAS  Google Scholar 

  • Ribatti D, Gualandris A, Bastaki M, Vacca, A, Lurlaro M, Roncali L, Presta M (1997a) New model for the study of angiogenesis and antiangiogenesis in the chick embryo chorioallantoic membrane: the gelatin sponge/chorioallantoic membrane assay. J Vasc Res 34:455–463

    PubMed  CAS  Google Scholar 

  • Ribatti D, Nico B, Bertossi M, Roncali L, Presta M (1997b) Basic fibroblast growth factor-induced angiogenesis in the chick embryo chorioallantoic membrane: an electron microscopy study, Microvasc Res 53:187–190

    PubMed  CAS  Google Scholar 

  • Ribatti D, Crivellato E, Candussio L, Vacca A, Nico B, Benagiano V, Roncali L, Dammacco F (2002) Angiogenic activity of rat mast cells in the chick embryo chorioallantoic membrane is down-regulated by treatment with recombinant human a2a interferon and partly mediated by fibroblast growth factor-2. Haematologica 87:465–471

    PubMed  CAS  Google Scholar 

  • Ridgway J, Zhang G, Wu Y, Stawicki S, Liang WC, Chanthery Y, Kowalski J, Watts RJ, Callahan C, Kasman I, Singh M, Chien M, Tan C, Hongo JA, de Sauvage F, Plowman G, Yan M (2006) Inhibition of D114 signalling inhibits tumour growth by deregulating angiogenesis. Nature 444:1083–1087

    PubMed  CAS  Google Scholar 

  • Rohan RM, Fernandez A, Udagawa T, Yuan J, D’Amato RJ (2000) Genetic heterogeneity of angiogenesis in mice. FASEB J 14:871–876

    PubMed  CAS  Google Scholar 

  • Rosenthal RA, Megyesi JF, Henzel WJ, Ferrara N, Folkman J (1990) Conditioned medium from mouse sarcoma 180 cells contains vascular endothelial growth factor. Growth Factors 4:53–59

    PubMed  CAS  Google Scholar 

  • Roy R, Wewer UM, Zurakowski D, Pories SE, Moses MA (2004) ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage. J Biol Chem 279:51323–51330

    PubMed  CAS  Google Scholar 

  • Rubin R, Casarett G (1966) Microcirculation of tumors. I. Anatomy, function and necrosis. Clin Radiol 17:220

    PubMed  CAS  Google Scholar 

  • Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–985

    PubMed  CAS  Google Scholar 

  • Shaked Y, Bertolini F, Man S, Rogers MS, Cervi D, Foutz T, Rawn K, Voskas D, Dumont DJ, Ben-David Y, Lawler J, Henkin J, Huber J, Hicklin DJ, D’Amato RJ, Kerbel RS (2005) Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis: implications for cellular surrogate marker analysis of antiangiogenesis. Cancer Cell 7:101–111

    PubMed  CAS  Google Scholar 

  • Shima DT, Adamis AP, Ferrara N, Yeo K-T, Yeo T-K, Allende R, Folkman J, D’Amore PA (1995) Hypoxic induction of endothelial cell growth factors in retinal cells: identification and characterization of vascular endothelial growth factor (VEGF) as the mitogen. Mol Med 1:182–193

    PubMed  CAS  Google Scholar 

  • Shing Y, Folkman J, Sullivan R, Butterfield C, Murray J, Klagsbrun M (1984) Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. Science 223:1296–1298

    PubMed  CAS  Google Scholar 

  • Shing Y, Folkman J, Haudenschild C, Lund D, Crum R, Klagsbrun M (1985) Angiogenesis is stimulated by a tumor-derived endothelial cell growth factor. J Cell Biochem 29:275–287

    PubMed  CAS  Google Scholar 

  • Sidky YA, Borden EC (1987) Inhibitors of angiogenesis by interferons: effects on tumorand lymphocyte-induced vascular responses. Cancer Res 47:5155–5161

    PubMed  CAS  Google Scholar 

  • Singh RK, Gutman M, Bucana CD, Sanchez R, Llansa N, Fidler IJ (1995) Interferons alpha and beta down-regulate the expression of basic fibroblast growth factor in human carcinomas. Proc Natl Acad Sci USA 92:4562–4566

    PubMed  CAS  Google Scholar 

  • Slaton JW, Perrotte P, Inoue K, Dinney CP, Fidler IJ (1999) Interferon-alpha-mediated down-regulation of angiogenesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule. Clin Cancer Res 5:2726–2734

    PubMed  CAS  Google Scholar 

  • Smith RS, Hawes NL, Kuhlmann SD, Heckenlively JR, Chang B, Roderick TH, Sundberg JP (1996) Cornl: a mouse model of corneal surface disease and neovascularization. Invest Ophthalmol Vis Sci 37:397–404

    PubMed  CAS  Google Scholar 

  • Stone EM (2006) A very effective treatment for neovascular macular degeneration. N Engl J Med 355:1493–1495

    PubMed  CAS  Google Scholar 

  • Suchting S, Freitas C, le Noble F, Benedito R, Breant C, Duarte A, Eichmann A (2007) The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proc Natl Acad Sci USA (in press)

    Google Scholar 

  • Tannock IF (1970) Population kinetics of carcinoma cells, capillary endothelial cells, and fibroblasts in a transplanted mouse mammary tumor. Cancer Res 30:2470

    PubMed  CAS  Google Scholar 

  • Taylor S, Folkman J (1982) Protamine is an inhibitor of angiogenesis. Nature 297:307–312

    PubMed  CAS  Google Scholar 

  • Teodoro JG, Parker AE, Zhu X, Green MR (2006) P53-mediated inhibition of angiogenesis through up-regulation of a collaghen prolyl hydroxylase. Science 313:968–971

    PubMed  CAS  Google Scholar 

  • Thiersch C (1865) Der Epithelialkrebs namentlich der Haut mit Atlas. Leipzig. As cited in Rogers W, Edlich RF, Lewis DV, Aust JB. Surg Clin North Am 47:1473

    Google Scholar 

  • Thiessen NW (1936) The vascularity of benign and malignant lesions of the stomach. Surg Gynecol Obstet 2:149

    Google Scholar 

  • Tjin Tham Sjin RM, Naspinsku J, Birsner AE, Li C, Chan R, Lo K, Gillies S, Folkman J, Samulski J, Javaherian K (2006) Endostatin therapy reveals a U-shaped curve for anti-tumor activity. Cancer Gene Ther 13:619–627

    PubMed  CAS  Google Scholar 

  • Toolan HW (1951) Proliferation and vascularization of adult human epithelium in subcutaneous tissues of x-irradiated heterologous hosts. Proc Soc Exp Biol Med 78:540

    PubMed  CAS  Google Scholar 

  • Udagawa T, Fernandez A, Achilles EG, Folkman J, D’Amato RJ (2002) Persistence of microscopic human cancers in mice: alterations in the angiogenic balance accompanies loss of tumor dormancy. FASEB J 16:1361–1370

    PubMed  CAS  Google Scholar 

  • Udagawa T, Puder M, Wood M, Schaefer BC, D’Amato RJ (2006) Analysis of tumor-associated stromal cells using SCID GFP transgenic mice: contribution of local and bone marrow-derived host cells. FASEB J 20:95–102

    PubMed  CAS  Google Scholar 

  • Verheul HMW, Lolkema MPJ, Qian DZ, Hilkes YHA, Liapi E, Pili R, Voest EE (2006) Uptake of bevacizumab by platelets blocks the biological activity of platelet-derived vascular endothelial growth actor (VEGF). Proceedings of the American Association of Cancer Research 47:5708 (abstract)

    Google Scholar 

  • Vlodavsky I, Folkman J, Sullivan R, Fridman R, Ishai-Michaeli R, Sasse J, Klagsbrun M (1987) Endothelial cell-derived basic fibroblast growth factor: Synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci USA 84:2292–2296

    PubMed  CAS  Google Scholar 

  • Warner L (1964) Frog renal adenocarcinoma: living vascular tree in ocular transplants. Anat Rec 148:425

    Google Scholar 

  • White CW, Sondheimer HM, Crouch EC, Wilson H, Fan LL (1989) Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. N Engl J Med 320:1197–1200

    PubMed  CAS  Google Scholar 

  • Yamamoto N, Kumashiro R (1993) Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by the stepwise action of beta-galactosidase of B cells and sialidase of T cells. J Immunol 151:2794–2802

    PubMed  CAS  Google Scholar 

  • Yang Q, Rasmussen SA, Friedman JM (2002) Mortality associated with Down’s syndrome in the USA from 1983 to 1997: A population-based study. Lancet 359:1019–1025

    PubMed  Google Scholar 

  • Zorick TS, Mustacchi Z, Bando SY, Zatz M, Moreira-Filho CA, Olsen B, Passos-Bueno MR (2001) High serum endostatin levels in Down syndrome: implications for improved treatment and prevention of solid tumours. Eur J Hum Genet 9:811–814

    PubMed  CAS  Google Scholar 

  • Zweifach BW (1961) Functional behavior of the microcirculation. Thomas, Springfield, Ill

    Google Scholar 

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  1. Karp Family Research Laboratories 12.129, Children’s Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115-5737, USA

    Judah Folkman MD

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  1. Judah Folkman MD
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  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)

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Folkman, J. (2008). Tumor Angiogenesis: from Bench to Bedside. In: Marmé, D., Fusenig, N. (eds) Tumor Angiogenesis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-33177-3_1

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