Subscribe to RSS
DOI: 10.1055/s-0037-1616232
Extracellular Proteolysis and Angiogenesis
Publication History
Publication Date:
12 December 2017 (online)
Summary
Extracellular proteolysis is an absolute requirement for new blood vessel formation, a process known as angiogenesis. This review will examine the role of the matrix metalloproteinase and plasminogen activator/plasmin systems during angiogenesis. Extracellular proteolysis has also been implicated in the generation of molecules with angioregulatory activity. These include, but are not limited to, angiostatin and endostatin. However, despite an abundance of data on their bioactivity, the molecular mechanisms by which these molecules achieve their effects are unknown. Anti-proteolysis, particularly in the context of angiogenesis, has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization.
-
References
- 1 Pepper MS. Manipulating angiogenesis: from basic science to the bedside. Arterioscler Thromb Vasc Biol 1997; 17: 605-19.
- 2 Andreasen PA, Egelund R, Petersen HH. The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol Life Sci 2000; 57: 25-40.
- 3 Vu TH, Werb Z. Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 2000; 14: 2123-33.
- 4 Keppler D, Sameni M, Moin K, Mikkelsen T, Diglio CA, Sloane BF. Tumor progression and angiogenesis: cathepsin B & Co. Biochem Cell Biol 1996; 74: 799-810.
- 5 Tamada Y, Fukiage C, Boyle DL, Azuma M, Shearer TR. Involvement of cysteine proteases in bFGF-induced angiogenesis in guinea pig and rat cornea. J Ocul Pharmacol Ther 2000; 16: 271-83.
- 6 Vlodavsky I, Elkin M, Pappo O, Aingorn H, Atzmon R, Ishai-Michaeli R, Aviv A, Pecker I, Friedmann Y. Mammalian heparanase as mediator of tumor metastasis and angiogenesis. Isr Med Assoc J 2000; 2 (Suppl) 37-45.
- 7 Bouck N. Tumor angiogenesis: the role of oncogenes and tumor suppressor genes. Cancer Cells 1990; 2: 179-85.
- 8 Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996; 86: 353-64.
- 9 Dvorak HF, Nagy JA, Feng D, Brown LF, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis. Curr Top Microbiol Immunol 1999; 237: 97-132.
- 10 Ferrara N. Vascular endothelial growth factor: molecular and biological aspects. Curr Top Microbiol Immunol 1999; 237: 1-30.
- 11 Dow JK, deVere White RW. Fibroblast growth factor 2: its structure and property, paracrine function, tumor angiogenesis, and prostate-related mitogenic and oncogenic functions. Urology 2000; 55: 800-6.
- 12 Gerwins P, Skoldenberg E, Claesson-Welsh L. Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis. Crit Rev Oncol Hematol 2000; 34: 185-94.
- 13 Pepper MS, Ferrara N, Orci L, Montesano R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophys Res Commun 1992; 189: 824-31.
- 14 Goto F, Goto K, Weindel K, Folkman J. Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels. Lab Invest 1993; 69: 508-17.
- 15 Asahara T, Bauters C, Zheng LP, Takeshita S, Bunting S, Ferrara N, Symes JF, Isner JM. Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo. Circulation 1995; 92 (Suppl. II) II-365-71.
- 16 Hu DE, Fan T-PD. Suppression of VEGF-induced angiogenesis by the protein tyrosine kinase inhibitor, lavendustin. A. Br J Pharmacol 1995; 114: 262-8.
- 17 Keshet E, Ben-Sasson SA. Anticancer drug targets: approaching angio-genesis. J Clin Invest 1999; 104: 1497-501.
- 18 Pepper MS, Montesano R. Proteolytic balance and capillary morphogenesis. Cell Differ Dev 1990; 32: 319-27.
- 19 Pepper MS, Montesano R, Mandriota SJ, Orci L, Vassalli JD. Angiogenesis: a paradigm for balanced extracellular proteolysis during cell migration and morphogenesis. Enzyme Protein 1996; 49: 138-62.
- 20 Montesano R, Pepper MS, Möhle-Steinlen U, Risau W, Wagner EF, Orci L. Increased proteolytic activity is responsible for the aberrant morphogenetic behaviour of endothelial cells expressing middle T oncogene. Cell 1990; 62: 435-45.
- 21 Woessner JF. The matrix metalloproteinase family. In: Matrix Metalloproteinases. Parks WC, Mecham RP. eds. San Diego: Academic Press; 1998: 1-14.
- 22 Johansson N, Ahonen M, Kähäri VM. Matrix metalloproteinases in tumor invasion. Cell Mol Life Sci 2000; 57: 5-15.
- 23 Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 2000; 1477: 267-83.
- 24 Seiki M. Membrane-type metalloproteinases. APMIS 1999; 107: 137-43.
- 25 Murphy G, Stanton H, Cowell S, Butler G, Knäuper V, Atkinson S, Gavrilovic J. Mechanisms for pro matrix metalloproteinase activation. APMIS 1999; 107: 38-44.
- 26 Stetler-Stevenson WG. Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest 1999; 103: 1237-41.
- 27 Raza SL, Cornelius LA. Matrix metalloproteinases: pro- and anti-angiogenic activities. J Investig Dermatol Symp Proc 2000; 5: 47-54.
- 28 Kräling BM, Wiederschain DG, Boehm T, Rehn M, Mulliken JB, Moses MA. The role of matrix metalloproteinase activity in the maturation of human capillary endothelial cells in vitro. J Cell Sci 1999; 112: 1599-609.
- 29 Zhu WH, Guo X, Villaschi S, Nicosia RF. Regulation of vascular growth and regression by matrix metalloproteinases in the rat aorta model of angiogenesis. Lab Invest 2000; 80: 545-55.
- 30 Lozonschi L, Sunamura M, Kobari M, Egawa S, Ding L, Matsuno S. Controlling tumor angiogenesis and metastasis of C26 murine colon adeno-carcinoma by a new matrix metalloproteinase inhibitor, KB-R7785, in two tumor models. Cancer Res 1999; 59: 1252-8.
- 31 Maekawa R, Maki H, Yoshida H, Hojo K, Tanaka H, Wada T, Uchida N, Takeda Y, Kasai H, Okamoto H, Tsuzuki H, Kambayashi Y, Watanabe F, Kawada K, Toda K, Ohtani M, Sugita K, Yoshioka T. Correlation of anti-angiogenic and antitumor efficacy of N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA), an orally-active, selective matrix metalloproteinase inhibitor. Cancer Res 1999; 59: 1231-5.
- 32 Fang J, Shing Y, Wiederschain D, Yan L, Butterfield C, Jackson G, Harper J, Tamvakopoulos G, Moses MA. Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model. Proc Natl Acad Sci USA 2000; 97: 3884-9.
- 33 Koivunen E, Arap W, Valtanen H, Rainisalo A, Medina OP, Heikkila P, Kantor C, Gahmberg CG, Salo T, Konttinen YT, Sorsa T, Ruoslahti E, Pasqualini R. Tumor targeting with a selective gelatinase inhibitor. Nat Biotechnol 1999; 17: 768-74.
- 34 Brooks PC, Silletti S, von Schalscha TL, Friedlander M, Cheresh DA. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell 1998; 92: 391-400.
- 35 Pfeifer A, Kessler T, Silletti S, Cheresh DA, Verma IM. Suppression of angiogenesis by lentiviral delivery of PEX, a noncatalytic fragment of matrix metalloproteinase 2. Proc Natl Acad Sci USA 2000; 97: 12227-32.
- 36 Silletti S, Kessler T, Goldberg J, Boger DL, Cheresh DA. Disruption of matrix metalloproteinase 2 binding to integrin alpha v beta 3 by an organic molecule inhibits angiogenesis and tumor growth in vivo. Proc Natl Acad Sci USA 2001; 98: 119-24.
- 37 Itoh T, Ikeda T, Gomi H, Nakao S, Suzuki T, Itohara S. Unaltered secretion of beta-amyloid precursor protein in gelatinase A (matrix metalloproteinase 2)-deficient mice. J Biol Chem 1997; 272: 22389-92.
- 38 Vu TH, Shipley JM, Bergers G, Berger JE, Helms JA, Hanahan D, Shapiro SD, Senior RM, Werb Z. MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes. Cell 1998; 93: 411-22.
- 39 Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, Itohara S. Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res 1998; 58: 1048-51.
- 40 Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nature Cell Biol 2000; 2: 737-44.
- 41 Holmbeck K, Bianco P, Caterina J, Yamada S, Kromer M, Kuznetsov SA, Mankani M, Robey PG, Poole AR, Pidoux I, Ward JM, Birkedal-Hansen H. MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 1999; 99: 81-92.
- 42 Zhou Z, Apte SS, Soininen R, Cao R, Baaklini GY, Rauser RW, Wang J, Cao Y, Tryggvason K. Impaired enchondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proc Natl Acad Sci USA 2000; 97: 4052-7.
- 43 Hosseini G, Butler GS, O’Connell JP, Soriano J, Montesano R, Docherty AJP, Overall CM, Pepper MS. Matrix metalloproteinase requirement during angiogenesis in vitro: a comparative study in collagen and fibrin gels. Manuscript submitted.
- 44 Anande-Apte B, Pepper MS, Voest E, Montesano R, Olsen B, Murphy G, Apte SS, Zetter B. Inhibition of angiogenesis by tissue inhibitor of metal-loproteinase-3 (TIMP-3). Invest Ophthalmol Vis Sci 1997; 38: 817-23.
- 45 Collen D. The plasminogen (fibrinolytic) system. Thromb Haemost 1999; 82: 259-70.
- 46 Montesano R, Pepper MS, Vassalli JD, Orci L. Phorbol ester induces cultured endothelial cells to invade a fibrin matrix in the presence of fibrinolytic inhibitors. J Cell Physiol 1987; 132: 509-16.
- 47 Hiraoka N, Allen E, Apel IJ, Gyetko MR, Weiss SJ. Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins. Cell 1998; 95: 365-77.
- 48 Hotary K, Allen E, Punturieri A, Yana I, Weiss SJ. Regulation of cell invasion and morphogenesis in a three-dimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3. J Cell Biol 2000; 149: 1309-23.
- 49 Carmeliet P, Collen D. Transgenic mouse models in angiogenesis and cardiovascular disease. J Pathol 2000; 190: 387-405.
- 50 Kroon ME, Koolwijk P, van Der Vecht B, van Hinsbergh VWM. Urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia: implications for capillary-like tube formation in a fibrin matrix. Blood 2000; 96: 2775-83.
- 51 Uchiyama T, Kurabayashi M, Ohyama Y, Utsugi T, Akuzawa N, Sato M, Tomono S, Kawazu S, Nagai R. Hypoxia induces transcription of the plasminogen activator inhibitor-1 gene through genistein-sensitive tyrosine kinase pathways in vascular endothelial cells. Arterioscler Thromb Vasc Biol 2000; 20: 1155-61.
- 52 Pepper MS, Vassalli J-D, Montesano R, Orci L. Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells. J Cell Biol 1987; 105: 2535-41.
- 53 Pepper MS, Sappino A-P, Montesano R, Orci L, Vassalli J-D. Plasminogen activator inhibitor-1 is induced in migrating endothelial cells. J Cell Physiol 1992; 153: 129-39.
- 54 Pepper MS, Sappino A-P, Stocklin R, Montesano R, Orci L, Vassalli J-D. Upregulation of urokinase receptor expression on migrating endothelial cells. J Cell Biol 1993; 122: 673-84.
- 55 Bacharach E, Itin A, Keshet E. Apposition-dependent induction of plasminogen activator inhibitor type-1 expression: a mechanism for balancing pericellular proteolysis during angiogenesis. Blood 1998; 92: 939-45.
- 56 Pepper MS. Lymphangiogenesis and tumor metastasis: myth or reality. Clin Cancer Res. 2001 in press.
- 57 Pepper MS, Wasi S, Ferrara N, Orci L, Montesano R. In vitro angiogenic and proteolytic properties of bovine lymphatic endothelial cells. Exp Cell Res 1994; 210: 298-305.
- 58 Pepper MS, Mandriota SJ, Jeltsch M, Kumar V, Alitalo K. Vascular endothelial growth factor (VEGF)-C synergises with basic fibroblast growth factor and VEGF in the induction of angiogenesis in vitro, and alters endothelial cell proteolytic properties. J Cell Physiol 1998; 177: 439-52.
- 59 Liu N-F, He Q-L. The regulatory effects of cytokines on lymphatic angio-genesis. Lymphology 1997; 30: 3-12.
- 60 Leak LV, Saunders M, Day AA, Jones M. Stimulation of plasminogen activator and inhibitor in the lymphatic endothelium. Microvasc Res 2000; 60: 201-11.
- 61 Rømer J, Bugge TH, Pyke C, Lund LR, Flick MJ, Degan LJ, Dan K. Impaired wound healing in mice with a disrupted plasminogen gene. Nature Med 1996; 2: 287-92.
- 62 Soff GA, Sanderowitz J, Gately S, Verrusio E, Weiss I, Brem S, Kwaan HC. Expression of plasminogen activator inhibitor type 1 by human prostate carcinoma cells inhibits primary tumor growth, tumor-associated angiogenesis, and metastasis to lung and liver in an athymic mouse model. J Clin Invest 1995; 96: 2593-600.
- 63 Heymans S, Luttun A, Nuyens D, Theilmeier G, Creemers E, Moons L, Dyspersin GD, Cleutjens JP, Shipley M, Angellilo A, Levi M, Nube O, Baker A, Keshet E, Lupu F, Herbert JM, Smits JF, Shapiro SD, Baes M, Borgers M, Collen D, Daemen MJ, Carmeliet P. Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nat Med 1999; 5: 1135-42.
- 64 Berman M, Winthrop S, Ausprunk D, Rose J, Langer R, Gage J. Plasminogen activator (urokinase) causes vascularization of the cornea. Invest Ophthalmol Vis Sci 1982; 22: 191-9.
- 65 Goldfarb RH, Ziche M, Murano G, Liotta LA. Plasminogen activators (urokinase) mediate neovascularization: possible role in tumor angiogenesis. Sem Thromb Hemost 1986; 12: 337-8.
- 66 Fibbi G, Caldini R, Chevanne M, Pucci M, Schiavone N, Morbidelli L, Parenti A, Granger HJ, Del Rosso M, Ziche M. Urokinase-dependent angio-genesis in vitro and diacylglycerol production are blocked by antisense oligonucleotides against the urokinase receptor. Lab Invest 1998; 78: 1109-19.
- 67 Ribatti D, Leali D, Vacca A, Giuliani R, Gualandris A, Roncali L, Nolli ML, Presta M. In vivo angiogenic activity of urokinase: role of endogenous fibroblast growth factor-2. J Cell Sci 1999; 112: 4213-21.
- 68 Min HY, Doyle LV, Vitt CR, Zandonella L, Stratton-Thomas JR, Shuman MA, Rosenberg S. Urokinase receptor antagonists inhibit angiogenesis and primary tumor growth in syngeneic mice. Cancer Res 1996; 56: 2428-33.
- 69 Li H, Lu H, Griscelli F, Opolon P, Sun LQ, Ragot T, Legrand Y, Belin D, Soria J, Soria C, Perricaudet M, Yeh P. Adenovirus-mediated delivery of a uPA/uPAR antagonist suppresses angiogenesis-dependent tumor growth and dissemination in mice. Gene Ther 1998; 5: 1105-13.
- 70 Evans CP, Elfman F, Parangi S, Conn M, Cunha G, Shuman MA. Inhibition of prostate cancer neovascularization and growth by urokinase-plasminogen activator receptor blockade. Cancer Res 1997; 57: 3594-9.
- 71 Guo Y, Higazi AA, Arakelian A, Sachais BS, Cines D, Goldfarb RH, Jones TR, Kwaan H, Mazar AP, Rabbani SA. A peptide derived from the nonreceptor binding region of urokinase plasminogen activator (uPA) inhibits tumor progression and angiogenesis and induces tumor cell death in vivo. FASEB J 2000; 14: 1400-10.
- 72 Mishima K, Mazar AP, Gown A, Skelly M, Ji XD, Wang XD, Jones TR, Cavenee WK, Huang HJ. A peptide derived from the non-receptor-binding region of urokinase plasminogen activator inhibits glioblastoma growth and angiogenesis in vivo in combination with cisplatin. Proc Natl Acad Sci USA 2000; 97: 8484-9.
- 73 Bajou K, Noel A, Gerard RD, Masson V, Brunner N, Holst-Hansen C, Skobe M, Fusenig NE, Carmeliet P, Collen D, Foidart JM. Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat Med 1998; 4: 923-8.
- 74 Gutierrez LS, Schulman A, Brito-Robinson T, Noria F, Ploplis VA, Castellino FJ. Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1. Cancer Res 2000; 60: 5839-47.
- 75 Loskutoff DJ, Curriden SA, Hu G, Deng G. Regulation of cell adhesion by PAI-1. APMIS 1999; 107: 54-61.
- 76 Ossowski L, Aguirre-Ghiso JA. Urokinase receptor and integrin partnership: coordination of signalling for cell adhesion, migration and growth. Curr Opinion Cell Biol 2000; 12: 613-20.
- 77 Preissner KT, Kanse SM, May AE. Urokinase receptor: a molecular organizer in cellular communication. Curr Opinion Cell Biol 2000; 12: 621-8.
- 78 Levin EG, del Zoppo GJ. Localization of tissue plasminogen activator in the endothelium of a limited number of vessels. Am J Pathol 1994; 144: 855-61.
- 79 Yasunaga C, Nakashima Y, Sueishi K. A role of fibrinolytic activity in angiogenesis. Quantitative assay using in vitro model. Lab Invest 1989; 61: 698-704.
- 80 Sato Y, Okamura K, Morimoto A, Hamanaka R, Hamaguchi K, Shimada T, Ono M, Kohno K, Sakata T, Kuwano M. Indispensable role of tissue-type plasminogen activator in growth factor-dependent tube formation of human microvascular endothelial cells in vitro. Exp Cell Res 1993; 204: 223-9.
- 81 Ito K-I, Ryuto M, Ushiro S, Ono M, Sugenoya A, Kuraoka A, Shibata Y, Kuwano M. Expression of tissue-type plasminogen activator and its inhibitor couples with development of capillary network by human microvascular endothelial cells on Matrigel. J Cell Physiol 1995; 162: 213-24.
- 82 Pepper MS, Rosnoblet C, Di Sanza C, Kruithof E. K. O. Synergistic induction of tissue-type plasminogen activator (tPA) by vascular endothelial growth factor and basic fibroblast growth factor and localization of tPA to Weibel-Palade bodies in bovine microvascular endothelial cells. Manuscript submitted.
- 83 Taraboletti G, Sonzogni L, Vergani V, Hosseini G, Ceruti R, Ghilardi C, Bastone A, Toschi E, Borsotti P, Scanziani E, Giavazzi R, Pepper MS, Stetler-Stevenson WG, Bani MR. Posttranscriptional stimulation of endothelial cell matrix metalloproteinases 2 and 1 by endothelioma cells. Exp Cell Res 2000; 258: 384-94.
- 84 O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Cao Y, Moses M, Lane WS, Sage EH, Folkman J. Angiostatin: a circulating endothelial cell inhibitor that suppresses angiogenesis and tumor growth. Cold Spring Harbor Symp Quant Biol 1994; 59: 471-82.
- 85 Cao Y. Therapeutic potentials of angiostatin in the treatment of cancer. Haematologica 1999; 84: 643-50.
- 86 Cirri L, Donnini S, Morbidelli L, Chiarugi P, Ziche M, Ledda F. Endostatin: a promising drug for antiangiogenic therapy. Int J Biol Markers 1999; 14: 263-7.
- 87 Colorado PC, Torre A, Kamphaus G, Maeshima Y, Hopfer H, Takahashi K, Volk R, Zamborsky ED, Herman S, Sarkar PK, Ericksen MB, Dhanabal M, Simons M, Post M, Kufe DW, Weichselbaum RR, Sukhatme VP, Kalluri R. Anti-angiogenic cues from vascular basement membrane collagen. Cancer Res 2000; 60: 2520-6.
- 88 Kamphaus GD, Colorado PC, Panka DJ, Hopfer H, Ramchandran R, Torre A, Maeshima Y, Mier JW, Sukhatme VP, Kalluri R. Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. J Biol Chem 2000; 275: 1209-15.
- 89 Maeshima Y, Colorado PC, Torre A, Holthaus KA, Grunkemeyer JA, Ericksen MB, Hopfer H, Xiao Y, Stillman IE, Kalluri R. Distinct anti-tumor properties of a type IV collagen domain derived from basement membrane. J Biol Chem 2000; 275: 21340-8.
- 90 Maeshima Y, Colorado PC, Kalluri R. Two RGD-independent alpha vbeta 3 integrin binding sites on tumstatin regulate distinct anti-tumor properties. J Biol Chem 2000; 275: 23745-50.
- 91 O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79: 315-28.
- 92 Cao Y, Ji RW, Davidson D, Schaller J, Marti D, Söhndel S, McCance SG, O’Reilly MS, Llinás M, Folkman J. Kringle domains of human angiostatin. J Biol Chem 1996; 271: 29461-7.
- 93 Cao Y, Chen A, An SSA, Ji RW, Davidson D, Cao Y. Llin·s M. Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth. J Biol Chem 1997; 272: 22924-8.
- 94 Cao R, Wu HL, Veitonmaki N, Linden P, Farnebo J, Shi GY, Cao Y. Suppression of angiogenesis and tumor growth by the inhibitor K1-5 generated by plasmin-mediated proteolysis. Proc Natl Acad Sci USA 1999; 96: 5728-33.
- 95 Ji WR, Barrientos LG, Llinás M, Gray H, Villarreal X, DeFord ME, Castellino FJ, Kramer RA, Trail PA. Selective inhibition by kringle 5 of human plasminogen on endothelial cell migration, an important process in angiogenesis. Biochem Biophys. Res Commun 1998; 247: 414-9.
- 96 Ji WR, Castellino FJ, Chang Y, Deford ME, Gray H, Villarreal X, Eghtedarzadeh K, Marti DN, Llinas M, Schaller J, Kramer RA, Trail PA. Characterization of kringle domains of angiostatin as antagonists of endothelial cell migration, an important process in angiogenesis. FASEB J 1998; 12: 1731-8.
- 97 Dong Z, Kumar R, Yang X, Fidler IJ. Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. Cell 1997; 88: 801-10.
- 98 Patterson BC, Sang QA. Angiostatin-converting enzyme activities of human matrilysin (MMP-7) and gelatinase B/Type IV collagenase (MMP-9). J Biol Chem 1997; 272: 28823-5.
- 99 Cornelius LA, Nehring LC, Harding E, Bolanowski M, Welgus HG, Kobayashi DK, Pierce RA, Shapiro SD. Matrix metalloproteinases generate angiostatin: effects on neovascularization. J Immunol 1998; 161: 6845-52.
- 100 Lijnen HR, Ugwu F, Bini A, Collen D. Generation of an angiostatin-like fragment from plasminogen by stromelysin-1 (MMP-3). Biochemistry 1998; 37: 4699-702.
- 101 Heidtmann HH, Nettelbeck DM, Mingels A, Jäger R, Welker HG, Knoter-mann RE. Generation of angiostatin-like fragments from plasminogen by prostate-specific antigen. Br J Cancer 1999; 81: 1269-73.
- 102 Morikawa W, Yamamoto K, Ishikawa S, Takemoto S, Ono M, Fukushi J, Naito S, Nozaki C, Iwanaga S, Kuwano M. Angiostatin generated by cathepsin D secreted by human prostate carcinoma cells. J Biol Chem 2000; 275: 38912-20.
- 103 Stathakis P, Fitzgerald M, Matthias LJ, Chesterman CN, Hogg PJ. Generation of angiostatin by reduction and proteolysis of plasmin. Catalysis by a plasmin reductase secreted by cultured cells. J Biol Chem 1997; 272: 20641-5.
- 104 Stathakis P, Lay AJ, Fitzgerald M, Schlieker C, Matthias LJ, Hogg PJ. Angiostatin formation involves disulfide bond reduction and proteolysis in kringle 5 of plasmin. J Biol Chem 1999; 274: 8910-6.
- 105 Gately S, Twardowski P, Stack MS, Patrick M, Boggio L, Cundiff DL, Schapner HW, Madison L, Volpert O, Bouck N, Enghild J, Kwaan HC, Soff GA. Human prostate carcinoma cells express enzymatic activity that converts human plasminogen to the angiogenesis inhibitor, angiostatin. Cancer Res 1996; 56: 4887-90.
- 106 Gately S, Twardowski P, Stack MS, Cundiff DL, Grella D, Castellino FJ, Enghild J, Kwaan HC, Lee F, Kramer RA, Volpert O, Bouck N, Soff GA. The mechanism of cancer-mediated conversion of plasminogen to the angio-genesis inhibitor, angiostatin. Proc Natl Acad Sci USA 1997; 94: 10868-72.
- 107 Sim BKL, O’Reilly MS, Liang H, Fortier AH, He W, Madsen JW, Lapcevich R, Nacy CA. A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer. Cancer Res 1997; 57: 1329-34.
- 108 Wu Z, O’Reilly MS, Folkman J, Shing Y. Suppression of tumor growth with recombinant murine angiostatin. Biochem Biophys Res Commun 1997; 236: 651-4.
- 109 Claesson-Welsh L, Welsh M, Ito N, Anand-Apte B, Soker S, Zetter B, O’Reilly M, Folkman J. Angiostatin induces endothelial cell apoptosis and activation of focal adhesion kinase independently of the integrin-binding motif RGD. Proc Natl Acad Sci USA 1998; 95: 5579-83.
- 110 Stack MS, Gately S, Bafeti LM, Enghild JJ, Soff GA. Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation. Biochem J 1999; 340: 77-84.
- 111 Barendsz-Janson AF, Griffioen AW, Muller AD, van Dam-Mieras MC, Hillen HF. In vitro tumor angiogenesis assays: plasminogen lysine binding site 1 inhibits in vitro tumor-induced angiogenesis. J Vasc Res 1998; 35: 109-14.
- 112 Griscelli F, Li H, Bennaceur-Griscelli A, Soria J, Opolon P, Soria C, Perricaudet M, Yeh P, Lu H. Angiostatin gene transfer: inhibition of tumor growth in vivo by blockage of endothelial cell proliferation associated with a mitosis arrest. Proc Natl Acad Sci USA 1998; 95: 6367-72.
- 113 Lucas R, Holmgren L, Garcia I, Jiminez B, Mandriota SJ, Borlat F, Sim BKL, Wu Z, Grau GE, Shing Y, Soff GA, Bouck N, Pepper MS. Multiple forms of angiostatin induce apoptosis in endothelial cells. Blood 1998; 92: 4730-41.
- 114 Moser TL, Stack MS, Asplin I, Enghild JJ, Hojrup P, Everitt L, Hubchak S, Schapner HW, Pizzo SV. Angiostatin binds ATP synthase on the surface of human endothelial cells. Proc Natl Acad Sci USA 1999; 96: 2811-6.
- 115 O’Reilly MS, Holmgren L, Chen C, Folkman J. Angiostatin induces and sustains dormancy of human primary tumors in mice. Nature Med 1996; 2: 689-92.
- 116 Lannutti BJ, Gately ST, Quevedo ME, Soff GA, Paller AS. Human angiostatin inhibits murine hemangioendothelioma tumor growth in vivo. Cancer Res 1997; 57: 5277-80.
- 117 Kirsch M, Strasser J, Allende R, Bello L, Zhang J, Black PMcL. Angiostatin suppresses malignant glioma growth in vivo. Cancer Res 1998; 58: 4654-9.
- 118 Cao Y, O’Reilly MS, Marshall B, Flynn E, Ji RW, Folkman J. Expression of angiostatin cDNA in a murine fibrosarcoma suppresses primary tumor growth and produces long-term dormancy of metastases. J Clin Invest 1998; 101: 1055-63.
- 119 Griscelli F, Li H, Cheong C, Opolon P, Bennaceur-Griscelli A, Vassal G, Soria J, Soria C, Lu H, Perricaudet M, Yeh P. Combined effects of radio-therapy and angiostatin gene therapy in glioma tumor model. Proc Natl Acad Sci USA 2000; 97: 6698-703.
- 120 Sacco MG, Caniatti M, Cato EM, Frattini A, Chiesa G, Ceruti R, Adorni F, Zecca L, Scanziani E, Vezzoni P. Liposome-delivered angiostatin strongly inhibits tumor growth and metastatization in a transgenic model of spontaneous breast cancer. Cancer Res 2000; 60: 2660-5.
- 121 O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997; 88: 277-85.
- 122 Sasaki T, Fukai N, Mann K, Göhring W, Olsen BR, Timpl R. Structure, function and tissue forms of the C-terminal globular domain of collagen XVIII containing the angiogenesis inhibitor endostatin. EMBO J 1998; 4249-56.
- 123 Wen W, Moses MA, Wiederschain D, Arbiser JL, Folkman J. The generation of endostatin is mediated by elastase. Cancer Res 1999; 59: 6052-6.
- 124 Felbor U, Dreier L, Bryant RAR, Ploegh HL, Olsen BR, Mothes W. Secreted cathepsin L generates endostatin from collagen XVIII. EMBO J 2000; 19: 1187-94.
- 125 Ferreras M, Felbor U, Lenhard T, Olsen BR, Delaissé JM. Generation and degradation of human endostatin proteins by various proteinases. FEBS Lett 2000; 486: 247-51.
- 126 Dhanabal M, Volk R, Ramchandran R, Simons M, Sukhatme VP. Cloning, expression and in vitro activity of human endostatin. Biochem Biophys Res Commun 1999; 258: 345-52.
- 127 Kruger EA, Duray PH, Tsokos MG, Venzon DJ, Libutti SK, Dixon SC, Rudek MA, Pluda J, Allegra C, Figg WD. Endostatin inhibits microvessel formation in the ex vivo rat aortic ring assay. Biochem Biophys Res Commun 2000; 268: 183-91.
- 128 Miosge N, Sasaki T, Timpl R. Angiogenesis inhibitor endostatin is a direct component of elastic fibres in vessel walls. FASEB J 1999; 13: 1743-50.
- 129 Chang Z, Choon A, Friedl A. Endostatin binds to blood vessels in situ independent of heparin sulfate and does not compete for fibroblast growth factor-2 binding. Am J Pathol 1999; 155: 71-6.
- 130 Sasaki T, Larsson H, Kreuger J, Salmivirta M, Claesson-Welsh L, Lindahl U, Hohenester E, Timpl R. Structural basis and potential role of heparin/heparan sulfate binding to the angiogenesis inhibitor endostatin. EMBO J. 1999 6240-8.
- 131 Hohenester E, Sasaki T, Olsen BR, Timpl R. Crystal structure of the angiogenesis inhibitor andostatin at 1.5 Å resolution. EMBO J 1998; 17: 1656-64.
- 132 Ständker L, Schrader M, Kanse SM, Jürgens M, Forssmann WG, Preissner KT. Isolation and characterization of the circulating form of human endostatin. FEBS Lett 1997; 420: 129-33.
- 133 Dhanabal M, Ramchandran R, Volk R, Stillman IE, Lombardo M, IruelaArispe ML, Simons M, Sukhatme VP. Endostatin: yeast production, mutants, and antitumor effect in renal cell carcinoma. Cancer Res 1999; 59: 189-97.
- 134 Taddei L, Chiarugi P, Brogelli L, Cirri P, Magnelli L, Raugei G, Ziche M, Granger HJ, Chiarugi V, Ramponi G. Inhibitory effect of full-length human endostatin on in vitro angiogenesis. Biochem Biophys Res Commun 1999; 263: 340-5.
- 135 Berger AC, Feldman AL, Gnant MFX, Kruger EA, Sim BKL, Hewitt S, Figg WD, Alexander HR, Libutti SK. The angiogenesis inhibitor, endostatin, does not affect murine cutaneous wound healing. J Surg Res 2000; 26-31.
- 136 Kim YM, Jang JW, Lee OH, Yeon J, Choi EY, Kim KW, Lee ST, Kwon YG. Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase 2. Cancer Res 2000; 60: 5410-3.
- 137 Sauter BV, Martinet O, Zhang WJ, Mandeli J, Woo SLC. Adenovirus-mediated gene transfer of endostatin in vivo results in high level of trans-gene expression and inhibition of tumor growth and metastases. Proc Natl Acad Sci USA 2000; 97: 4802-7.
- 138 Joki T, Machluf M, Atala A, Zhu J, Seyfried NT, Dunn IF, Abe T, Carroll RS, Black PMcL. Continuous release of endostatin from microencapsulated engineered cells for tumor therapy. Nature Biotechnol 2001; 19: 35-9.
- 139 Yamaguchi N, Anand-Apte B, Lee M, Sasaki T, Fukai N, Shapiro R, Que I, Lowik C, Timpl R, Olsen BR. Endostatin inhibits VEGF-induced endothelial cell migration and tumor growth independently of zinc binding. EBMO J 1999; 4414-23.
- 140 Dhanabal M, Ramchandran R, Waterman MJF, Lu H, Knebelmann B, Segal M, Sukhatme VP. Endostatin induces endothelial cell apoptosis. J Biol Chem 1999; 274: 11721-6.
- 141 Yokoyama Y, Dhanabal M, Griffioen AW, Sukhatme VP, Ramakrishnan S. Synergy between angiostatin and endostatin: inhibition of ovarian cancer growth. Cancer Res 2000; 60: 2190-6.
- 142 Blezinger P, Wang J, Gondo M, Quezada A, Mehrens D, French M, Singhal A, Sullivan S, Rolland A, Ralston R, Min W. Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene. Nature Biotechnol 1999; 17: 343-8.
- 143 Bloch W, Huggel K, Sasaki T, Grose R, Bugnon P, Addicks K, Timpl R, Werner S. The angiogenesis inhibitor endostatin impairs blood vessel maturation during wound healing. FASEB J 2000; 14: 2373-6.
- 144 Perletti G, Concari P, Giardini R, Marras E, Piccinini Folkman J, Chen L. Antitumor activities of endostatin against carcinogen-induced rat primary mammary tumors. Cancer Res 2000; 60: 1793-6.
- 145 Yoon SS, Eto H, Lin C, Nakamura H, Pawlik TM, Song SU, Tanabe KK. Mouse endostatin inhibits the formation of lung and liver metastases. Cancer Res 1999; 59: 6251-6.
- 146 Feldman AL, Restifo NP, Alexander HR, Bartlett DL, Hwu P, Seth P, Libutti SK. Antiangiogenic gene therapy of cancer utilizing a recombinant adenovirus to elevate systemic endostatin levels in mice. Cancer Res 2000; 60: 1503-6.
- 147 Read TA, Sorensen DR, Mahesparan R, Enger Po, Timpl R, Olsen BR, Hjelstuen MHB, Haraldseth O. Bjerkvig. Local endostatin treatment of gliomas administered by microencapsulated producer cells. Nature Biotechnol 2001; 19: 29-34.
- 148 Boehm T, Folkman J, Browder T, O’íReilly MS. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 1997; 390: 4047.
- 149 Moulton KS, Heller E, Konerding MA, Flynn E, Palinski W, Folkman J. Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 1999; 99: 1726-32.
- 150 Mauceri HJ, Hanna NN, Beckett MA, Gorski DH, Staba MJ, Stellato KA, Bigelow K, Heimann R, Gately S, Dhanabal M, Soff GA, Sukhatme VP, Kufe DW, Weichselbaum RR. Combined effects of angiostatin and ionizing radiation in antitumor therapy. Nature 1998; 394: 287-91.
- 151 Gorski DH, Mauceri HJ, Salloum RM, Gately S, Hellman S, Beckett MA, Sukhatme VP, Soff GA, Kufe DW, Weichselbaum RR. Potentiation of the antitumor effect of ionizing radiation by brief concomitant exposures to angiostatin. Cancer Res 1998; 58: 5686-9.
- 152 Griffioen AW, Molema G. Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol Rev 2000; 52: 237-68.
- 153 Brown PD. Clinical studies with matrix metalloproteinase inhibitors. APMIS 1999; 107: 174-80.