Abstract
An increasing body of evidence indicates that in the leech Hirudo medicinalis the angiogenic process is finely regulated and coordinated by the botryoidal tissue. In this paper we provide evidence on the involvement of botryoidal tissue cells in angiogenesis induced in H. medicinalis by a variety of stimuli including surgical wounds or the administration of modulators of neovascularization. Interestingly, we show that either human activators of vascular cell growth, or anti-angiogenic peptides like angiostatin and endostatin, or the drug mitomycin, can induce a prompt biological response in H. medicinalis. We show as well that angiogenesis in this invertebrate shares a surprising degree of similarity with neovascularization in vertebrates, both at the biochemical and cellular levels, because it involves similar growth factors/growth factor receptors, and relies on analogous cell–cell or cell–matrix interactions. For these reasons we suggest that H. medicinalis can be used as a reproducible model for testing activators or inhibitors of angiogenesis, and for investigating the biochemical, ultrastructural and cellular processes involved in new vessel formation.
References
Mann KH. Leeches (Hirudinea): Their Structure, Physiology, Ecology and Embryology. Oxford: Pergamon Press 1962.
Sawyer RT. Leech Biology and Behavior 1: Anatomy, Physiology and Behaviour. Oxford: Oxford Scientific Publications 1986.
Sawyer RT, Fitzgerald SW. Leech Biology. Vol 1. Oxford: Oxford University Press 1981.
Fischer E. The myelo-erythroid nature of the chloragogenous-like tissues of the annelids. Comp Biochem Physiol 1993; 106: 449–53.
Bradbury S. The botryoidal and vaso-fibrous tissue of the leech Hirudo medicinalis. Quart J Microsc Sci 1959; 100: 483–98.
de Eguileor M, Grimaldi A, Tettamanti G et al. Ultrastructural and functional versatility of the hirudinean botryoidal tissue. Tissue & Cell 2001; 33: 332–41.
Bussolino F, Wang JM, Defilippi P et al. Granulocyte-and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature 1989; 337: 471–3.
Santamaria JA, Marí-Beffa M, Santos-Ruiz L et al. Incorporation of bromodeoxyuridine in regenerating fin tissue of the goldfish Carassius auratus. J Exp Zool 1996; 275: 300–7.
Moore RD, Mumaw V, Shonberg MD. Optical microscopy of ultrathin tissue sections. J Ultrastruct Res 1960; 4: 113–6.
Miller JB, Aidley DJ. Two rates of relaxation in the dorsal longitudinal muscle of leech. J Exp Biol 1973; 58: 91–103.
Geiger B, Tokuyasu KT, Dutton A et al. Vinculin an intracellular protein localized at specialized sites where microfilament bundles terminate at cell membranes. Proc Natl Acad Sci USA 1980; 77: 4127–31.
Barth PJ, Weingartner K, Kohler HH et al. Assessment of the vascularization in prostatic carcinoma: A morphometric investigation. Human Pathol 1996; 27: 1306–10.
Weibel ER. Stereological Methods. I. Practical Methods for Biological Morphometry. London: Academic Press 1979.
Cruz-Orive LM, Weibel ER. Recent stereological methods for cell biology. A brief survey. Am J Physiol 1990; 258: L148–56.
Beck L, D'Amore PA. Vascular development: Cellular and molecular regulation. FASEB J 1997; 11: 365–73.
Brooks PC, Montgomery AMP, Rosenfeld M et al. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenicblood vessels. Cell 1994; 79: 1157–64.
Carmeliet P. Mechanism of angiogenesis and arteriogenesis. Nat Med 2000; 6: 389–95.
Ruoslahti E, Engvall E. Integrins and vascular extracellular matrix assembly. J Clin Invest 1997; 99: 1149–52.
Wayner EA, Orlando RA, Cheresh DA. Integrins alpha v beta 3 and alpha v beta 5 contribute to cell attachment to vitronectin but differentially distribute on the cell surface. J Cell Biol 1991; 113: 919–29.
Enenstein J, Kramer RH. Confocal microscopic analysis of integrin expression on the microvasculature and its sprouts in the neonatal foreskin. J Invest Dermatol 1994; 103: 381–6.
Ingber DE. Fibronectin controls capillary endothelial cell growth by modulating cell shape. Proc Natl Acad Sci USA 1990; 87: 3579–83.
Clark RAF. Regulation of fibroplasia in cutaneous wound repair. Am J Med Sci 1993; 306: 42–8.
Jiang WG, Hiscox S. Hepatocyte growth factor/scatter factor, a cytokine playing multiple and converse roles. Histol Histopathol 1997; 12: 537–55.
Landeen LK, Ziegler FC, Halberstadt C. Characterization of a human dermal replacement. Wounds 1992; 5: 167–75.
Kim JK, Bing I, Armanini M et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993; 362: 841–46.
Senger DR, Claffey KP, Benes JE et al. Angiogenesis promoted by vascular endothelial growth factor: regulation through alpha 1 beta 1 and alpha 2 beta 2 integrins. Proc Natl Acad Sci USA 1997; 94: 13612–17.
Neufeld G, Gospodarowicz D. Basic and acidic fibroblast growth factors interact with the same cell surface receptors. J Biol Chem 1986; 261: 5631–7.
Rahmoune H, Chen H, Gallagher JT et al. Interaction of heparan sulfate from mammary cells with acidic fibroblast growth factor (FGF) and basic FGF. J Biol Chem 1998; 273: 7303–10.
de Eguileor M, Tettamanti G, Grimaldi A et al. Histopathological changes after induced injury in leeches. J Invert Pathol 1999; 74: 14–28.
Vlodavsky I, Fuks Z, Ishai-Michaeli R et al. Extracellular matrixresident basic fibroblast growth factor: implication for the control of angiogenesis. J Cell Biochem 1991; 45: 167–76.
Moses MA, Klagsbrun M, Shing Y. The role of growth factors in vascular cell development and differentiation. Int Rev Cytol 1995; 161: 1–48.
Carmeliet P, Collen D. Role of vascular endothelial growth factor and vascular endothelial growth factor receptors in vascular development. Curr Top Microbiol Immunol 1999; 237: 133–158.
Shimo T, Nakanishi T, Nishida T et al. Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo. J Biochem 1999; 126: 137–45.
Friedlander M, Theesfeld CL, Sugita M et al. Involvement of integrins alpha v beta 3 and alpha v beta 5 in ocular neovascular diseases. Proc Natl Acad Sci USA 1996; 93: 9764–69.
Brevini-Gandolfi TAL, Cillo F, Favetta LA et al. Somatostatin up-regulates Topoisomerase II Alpha expression and affects LNCaP cell cycle. Mol Cell Endocrinol 2001; 176: 103–10.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
de Eguileor, M., Grimaldi, A., Tettamanti, G. et al. Hirudo medicinalis: A new model for testing activators and inhibitors of angiogenesis. Angiogenesis 4, 299–312 (2001). https://doi.org/10.1023/A:1016025803370
Issue Date:
DOI: https://doi.org/10.1023/A:1016025803370