Angiogenesis Research Antibodies

Introduction

Embryonic vascular system undergoes a series of complex, highly regulated series of events involving differentiation, migration and association of primitive endothelial cells. This process is termed vasculogenesis. A further remodeling of the primitive vascular system forms the mature cardiovascular system. This process is known as angiogenesis (sprouting of new capillary vessels from pre-existing vasculature). Angiogenesis accounts for the formation of vasculature into previously avascular organs such as brain and kidney. Angiogenic activity in the adult is required during the normal tissue repair, and for the remodeling of the female reproductive organs (ovulation and placental development). Certain pathological conditions, such as tumor growth and diabetic retinopathy, also require angiogenesis. Recent studies have identified several proteolytic fragments or cryptic domains of proteins that act as inhibitors of angiogenesis. These include fragments of plasminogen such as Angiostatin protein (kringles 1-4) and kringles 1-5, C-terminal proteolytic fragment of Collagen XVIII (Endostatin protein), the NC10 domain of collagen 15 (Restin), the C-terminal hemopexin-like domain of MMP-2 (PEX), the N-terminal fragment of prolactin, and the N-terminally truncated platelet factor. The 20 kDa fragment of Collagen XVIII known as Endostatin protein inhibits tumor progression and induction of endothelial cell apoptosis. Administration of Endostatin protein to mice bearing certain tumors caused tumor regression without the development of drug resistance. Endostatin protein also inhibited systemic angiogenesis, primary tumor growth, and the development of primary metastatic lesions. It also reduced the levels of antiapoptotic proteins Bcl-2 and Bcl-xL and an increase in apoptosis of endothelial cells in vitro.

Angiostatin protein, a proteolytic fragment of plasminogen, is comprised of the first four kringle regions. It prevents the growth of endothelial cells, and its systemic administration inhibits the growth of primary carcinomas in mice. Kringles 1-3 fragment has a greater inhibitory activity than the kringles 1-4 fragment. The protease-activated kringles 1-5 is the most potent plasminogen fragment with over 50-fold greater endothelial cell specific inhibitory activity. Its systemic administration inhibited the growth of fibrosarcoma and significantly reduced neovascularization.

Angiogenin is a single polypeptide chain of 123 aa (mol wt ~14 kDa) secreted by tumor cells. It is a potent inhibitor of neovascularization. It specifically binds to endothelial cells and elicits second messenger systems. It has ribonucleolytic activity and is 33% identical to pancreatic RNAse A. Angiogenin has also been shown to undergo nuclear translocation in endothelial cells via receptor-mediated endocytosis and nuclear localization sequence-assisted nuclear import. Human and mouse angiogenin are 76% identical. The critical catalytic residues of human angiogenin are conserved in the mouse protein, as are the six cysteines necessary for disulfide bond formation.

Antibodies to Angiostatin, Endostatin and Angiogenin

Acris Antibodies offers an antibody panel for detection of Angiostation, Endostatin and Angiogenin useful for immunohistochemistry, western blotting and ELISA techniques.

Available Antibody Panel to Angiogenesis Research

Anti- Angiostatin (Plasminogen Precursor), Endostatin, Angiogenin antibody

Literature

Basile, D. P. (2004) Angiostatin and matrix metalloprotease expression following ischemic acute renal failure Am J Physiol Renal Physiol, May 2004; 286: 893 - 902

Hatziapostolou M., (2003) Different inhibitors of plasmin differentially affect angiostatin production and angiogenesis European Journal of Pharmacology 460, 1-8

Fett, J.W. et al. (1985) Isolation and Characterization of Angiogenin, an angiogenic Protein from Human Carcinoma Cells. Biochemistry: 24, 5480-5486.

Shapiro, R. & Vallee, B.L. (1987) Human placental ribonuclease inhibitor abolishes both angiogenic and ribonucleolytic activities of angiogenin. Proc. Natl. Acad. Sci. 84, 2238-2241.

Kurachi, K., et al. (1985) Sequence of the cDNA and Gene for Angiogenin, a human Angiogenesis Factor. Biochemistry: 24 5494-5499

O'Reilly, et al. (1997): Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88: 277-285 O'Reilly, et al.(1994) Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79: 315-328

Karumanchi, S. A.;et al. (2001) Cell surface glypicans are low-affinity endostatin receptors. Molec. Cell 7: 811-822 Sertie, A. L.; et al. (2000) Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome). Hum. Molec. Genet. 9: 2051-2058

Distler, H. J. Et al. (2003) Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med. 47(3):149-61.

Albitar, M. (2001) Angiogenesis in acute myeloid leukemia and myelodysplastic syndrome. Acta Haematol. 106(4):170-6.

Riordan JF and Shapiro R.Isolation and enzymatic activity of angiogenin. Methods Mol Biol. 2001;160:375-85.