Abstract
The formation of new blood vessels from existing blood vessels has been referred to as angiogenesis to distinguish the process from de novo embryonic vessel formation or vasculogenesis (1). This chapter will describe an in vivo assay to measure angiogenesis. There are several important reasons to study and measure angiogenesis in vascular disease. First, it is necessary to try to understand proliferative angiogenesis as it occurs in tumors and in diabetic complications and devise strategies to inhibit it. Second, there is intense interest in improving angiogenesis after ischemia or in chronic wounds (2). Third, many potential modulators of angiogenesis need to be evaluated to determine their effects on blood vessel development.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Folkman, J. (1995) Angiogenesis in cancer, vascular rheumatoid and other diseases. Nat. Med. 1, 27ā30.
Melillo, G., Scoccianti, M., Kovesdi, I., Safi, J. Jr., Riccioni, T., and Capogrossi, M. C. (1997) Gene therapy for collateral vessel development. Cardiovasc. Res. 35, 480ā489.
Knighton, D. R. and Fiegel, V. D. (1991) Regulation of cutaneous wound healing by growth factors and the micro-environment. Invest. Radiol. 26, 604ā611.
Quesada, A. R., Barbacid, M. M., Mira, E., Fernandez-Resa, P., Marquez, G., and Aracil, M. (1997) Evaluation of fluorometric and zymographic methods as activity assays for stromelysins and gelatinases. Clin. Exp. Metastasis 15, 339,340.
Albini, A., Iwamoto, Y., Kleinman, H. K., Martin, G. R., Aaronson, S. A., Kozlowski, J. M., and McEwan, R. N. (1987) A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 47, 3239ā3245.
Varner, J. A., Brooks, P. C., and Cheresh, D. A. (1995) REVIEW: the integrin alpha V beta 3: angiogenesis and apoptosis. Cell. Adhes. Commun. 3, 367ā374.
Norrby, K. (1997) Mast cells and de novo angiogenesis: angiogenic capability of individual mast-cell mediators such as histamine, TNF, IL-8 and bFGF. Inflamm. Res. 46, S7,8.
Brown, L. F., Detmar, M., Claffey, K., Nagy, J. A., Feng, D., Dvorak, A. M., and Dvorak, H. F. (1997) Vascular permeability factor/vascular endothelial growth factor: a multifunctional angiogenic cytokine. EXS 79, 233ā269.
Maisonpierre, P. C., Suri, C., Jones, P. F., Bartunkova, S., Wiegand, S. J., Radziejewski, C., et al. (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277, 55ā60.
Klagsbrun, M. and DāAmore, P. A. (1991) Regulators of angiogenesis. Annu. Rev. Physiol. 53, 217ā239.
Grant, D. S., Tashiro, K., Segui-Real, B., Yamada, Y., Martin, G. R., and Kleinman, H. K. (1989) Two different laminin domains mediate the differentiation of human endothelial cells into capillary-like structures in vitro. Cell 58, 933ā943.
Yoshida, S., Ono, M., Shono, T., Izumi, H., Ishibashi, T., Suzuki, H., and Kuwano, M. (1997) Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. Mol. Cell. Biol. 17, 4015ā4023.
Hanahan, D. (1997) Signaling vascular morphogenesis and maintenance. Science 277, 48ā50.
OāReilly, M. S., Holmgren, L., Shing, Y., Chen, C., Rosenthal, R. A., Moses, M., et al. (1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79, 315ā328.
OāReilly, M. S., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W. S., et al. (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88, 277ā285.
Gimbrone, M. A., Cotran, R. S., Leapman, S. B., and Folkman, J. (1974) Tumor growth and neovascularization: an experimental model using the rabbit cornea. J. Natl. Cancer Inst. 52, 413.
Ausprunk, D. H., Knighton, D. R., and Folkman, J. (1975) Vascularization of normal and neoplastic tissues grafted to the chick chorioallantois: role of host and pre-existing graft blood vessels. Am. J. Pathol. 79, 597.
Muthukaruppan, V. R. and Auerbach R. (1979) Angiogenesis in the mouse cornea. Science 205, 1416.
Folkman, J. and Haudenschild, C. (1980) Angiogenesis in vitro. Nature 288, 551ā556.
Nicosia, R. F. and Madri, J. A. (1987) The microvascular extracellular matrix: developmental changes during angiogenesis in the aortic ring-plasma clot model. Am. J. Pathol. 128, 78ā90.
Kubota, Y., Kleinman, H. K., Martin, G. R., and Lawley, T. J. (1988) Role of laminin and basement membrane in the differentiation of human endothelial cells into capillary-like structures. J. Cell. Biol. 107, 1589ā1597.
Thompson, J. A., Anderson, K. D., DiPietro, J. M., Zwiebel, J. A., Zametta, M., Anderson, W. F., and Maciag, T. (1988) Site-directed neovessel formation in vivo. Science 241, 1349ā1352.
Grant, D. S., Tashiro, K., Segui-Real, B., Yamada, Y., Martin, G. R., and Kleinman, H. K. (1989) Two different laminin domains mediate the differentiation of human endothelial cells into capillary-like structures in vitro. Cell 58, 933ā943.
Mignatti, P., Tsuboi, R., Robbins, E., and Rifkin D. B. (1989) In vitro angiogenesis on the human amniotic membrane: requirement for basic fibroblast growth factor-induced proteinases. J. Cell Biol. 108, 671ā682.
Plunkett, M. L. and Hailey, J. A. (1990) An in vivo quantitative angiogenesis model using tumor cells entrapped in alginate. Lab. Invest. 62, 510ā517.
Iruela-Arispe, M. L., Hasselaar, P., and Sage, H. (1991) Differential expression of extracellular proteins is correlated with angiogenesis in vitro. Lab. Invest. 64, 174ā186.
Passaniti, A., Taylor, R. M., Pili, R., Guo Y., Long, P. V., Haney, J.A., Pauly, R. R., Grant, D. S., and Martin, G. R. (1992) A simple, quantitative method for assessing angiogenesis and anti-angiogenic agents using reconstituted basement membrane, heparin, and FGF. Lab. Invest. 67, 519ā528.
Brown, K. J., Maynes, S. F., Bezos, A., Maguire, D. J., Ford, M. D., and Parish, C. R. (1996) A novel in vitro assay for human angiogenesis. Lab. Invest. 75, 539ā555.
Jain, R. K., Schlenger, K., Hockel, M., and Yuan, F. (1997) Quantitative angiogenesis assays: progress and problems. Nature Med. 3, 1203ā1208.
Swarm, R. L. (1963) Transplantation of a murine chondrosarcoma in mice of different inbred strains. J. Natl. Cancer Inst. 31, 953ā974.
Kleinman, H. K., McGarvey, M. L., Hassell, J. R., Star, V. L., Cannon, F. B., Laurie, G. W., and Martin, G. R. (1986) Basement membrane complexes with biological activity. Biochemistry 25, 312ā318.
DeLisser, H.. M, Christofidou-Solomidou, M., Strieter, R. M., Burdick, M. D., Robinson, C. S., Wexler, R. S., et al. (1997) Involvement of endothelial PECAM-1/CD31 in angiogenesis. Am. J. Pathol. 151, 671ā677.
Kibbey, M. C., Grant, D. S., and Kleinman, H. K. (1992) Role of the SIKVAV site of laminin in promotion of angiogenesis and tumor growth: an in vivo Matrigel model. J. Natl. Cancer Inst. 84, 1633ā1638.
Vukanovic, J., Passaniti, A., Hirato, T., Traysman, R. J., and Isaacs, J. T. (1992) Antiangiogenic effects of the Quinoline-3-carboxamide, linomide. Cancer Res. 53, 1833ā1837.
Grant, D. S., Kleinman, H. K., Goldberg, I. D., Bhargava, M. M., Nickoloff, B. J., Kinsella, J. L., et al. (1993) Scatter factor induces blood vessel formation in vivo. Proc. Natl. Acad. Sci. USA 90, 1937ā1941.
Pili, R., Guo, Y., Chang, J., T., Nakanishi, H., Martin, G. R., and Passaniti, A. (1994) Altered angiogenesis underlying age-dependent changes in tumor growth86, 1303ā1314.
Pili, R., Chang, J., Partis, R. A., Mueller, R. A., Novick, T., Chrest, F. J., and Passaniti, A. (1995) The Ī±-glucosidase inhibitor castanospermine alters endothelial cell glycosylation, prevents angiogenesis, and inhibits tumor growth. Cancer Res. 55, 2920ā2926.
Muhlhauser, J., Merrill, M. J., Pili, R., Maeda, H., Bacic, M., Bewig, B., Passaniti, A., et al. (1995) VEGF165 expressed by replication deficient recombinant adenovirus vector induces angiogenesis in vivo. Cir. Res. 77, 1077ā1086.
Muhlhauser, J., Pili, R., Merrill, M.J., Maeda, H., Passaniti, A., Crystal, R. G., and Capogrossi, M. C. (1995) In vivo angiogenesis induced by recombinant adenovirus vectors coding either for secreted or non-secreted forms of acidic fibroblast growth factor. Human Gene Ther. 6, 1457ā1465.
Taraboletti, G., Garofalo, A., Belotti, D., Drudis, T., Borsotti, P., Scanziani, E., Brown, P, D., and Giavazzi R. (1995) Inhibition of angiogenesis and murine hemangioma growth by batimastat, a synthetic inhibitor of matrix metallo-proteinases. J. Natl. Cancer Inst. 87, 293ā298.
Angiolillo, A. L., Sgadari, C., Taub, D. D., Liao, F., Farber, J. M., Maheshwari, S., et al. (1995) Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo. J. Exp. Med. 182, 155ā162.
Bussolino, F., Arese, M., Montrucchio, G., Barra, L., Primo, L., Benelli, R., et al. (1995) Platelet activating factor produced in vitro by Kaposiās sarcoma cells induces and sustains in vivo angiogenesis. J. Clin. Invest. 96, 940ā952.
Camussi, G., Montrucchio, G., Lupia, E., De Martino, A., Perona, L., Arese, M., et al. (1995) Platelet-activating factor directly stimulates in vitro migration of endothelial cells and promotes in vivo angiogenesis by a heparin-dependent mechanism. J. Immunol. 154, 6492ā6501.
Corallini, A., Campioni, D., Rossi, C., Albini, A., Possati, L., Rusnati, M., et al. (1996) Promotion of tumour metastases and induction of angiogenesis by native HIV-1 Tat protein from BK virus/tat transgenic mice. AIDS 10, 701ā710.
Biancone, L., Martino, A. D., Orlandi, V., Conaldi, P. G., Toniolo, A., and Camussi, G. (1997) Development of inflammatory angiogenesis by local stimulation of Fas in vivo. J. Exp. Med. 186, 147ā152.
Haralabopoulos, G. C., Grant, D. S., Kleinman, H. K., and Maragoudakis, M. E. (1997) Thrombin promotes endothelial cell alignment in Matrigel in vitro and angiogenesis in vivo. Am. J. Physiol. 273, 239ā245.
Angiolillo, A. L., Kanegane, H., Sgadari, C., Reaman, G. H., and Tosato, G. (1997) Interleukin-15 promotes angiogenesis in vivo. Biochem. Biophys. Res. Commun. 233, 231ā237.
Montrucchio, G., Lupia, E., de Martino, A., Battaglia, E., Arese, M., Tizzani, A., Bussolino, F., ad Camussi, G. (1997) Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha. Am. J. Pathol. 151, 557ā563.
Wilson, M. J. and Sinha, A. A. (1997) Human prostate tumor angiogenesis in nude mice: metalloprotease and plasminogen activator activities during tumor growth and neovascularization of subcutaneously injected matrigel impregnated with human prostate tumor cells. Anat. Rec. 249, 63ā73.
Pili, R., Chang, J., Muhlhauser, J., Crystal, R. G., Capogrossi, M. C., and Passaniti, A. (1997) Adenovirus-mediated gene transfer of fibroblast growth factor-1: angiogenesis and tumorigenicity in nude mice. Int. J. Cancer 73, 258ā263.
Riccioni, T., Cirielli, C., Wang, X., Passaniti, A., and Capogrossi, M. (1998) Adenovirus-mediated wild-type p53 overexpression inhibits endothelial cell differentiation in vitro and angiogenesis in vivo. Gene Ther. 5, 747ā754.
Skobe, M., Rockwell, P., Goldstein, N., Vosseler, S., and Fusenig, N. E. (1997) Halting angiogenesis suppresses carcinoma cell invasion. Nat. Med. 3, 1222ā1227.
Auerbach, R., Morrissey, L. W., and Sidly, Y. A. (1978) Regional differences in the incidence and growth of mouse tumors following intradermal or subcutaneous inoculation. Cancer Res. 38, 1739ā1744.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
Ā© 1999 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Capogrossi, M.C., Passaniti, A. (1999). An In Vivo Angiogenesis Assay to Study Positive and Negative Regulators of Neovascularization. In: Baker, A.H. (eds) Vascular Disease. Methods in Molecular Medicineā¢, vol 30. Humana Press. https://doi.org/10.1385/1-59259-247-3:367
Download citation
DOI: https://doi.org/10.1385/1-59259-247-3:367
Publisher Name: Humana Press
Print ISBN: 978-0-89603-731-1
Online ISBN: 978-1-59259-247-0
eBook Packages: Springer Protocols