Control of angiogenesis by heparin and other sulfated polysaccharides.

Heparin and its related polysaccharides are revealed to have important new functions as regulators of blood vessel growth and regression. This regulatory activity may be explained in part by at least five mechanisms in which heparin and heparan sulfate interact with peptide growth factors: (1) Heparin and heparan sulfate have a high affinity for angiogenic growth factors such as the fibroblast growth factors and VEGF, as well as for angiogenic inhibitors such as thrombospondin and platelet factor 4. (2) Heparin and its related polysaccharides stabilize bFGF and other growth factors. (3) FGFs and thrombospondin are stored in the extracellular matrix bound to heparan sulfate; fragments of heparin or heparan sulfate may act as natural chaperones to shuttle bFGF or other growth factors to different cellular compartments. (5) Heparin-like low-affinity receptors on the surface of endothelial cells (and other cells), prepare FGFs for binding to their specific high affinity receptors; and (6) Heparin and its related polysaccharides potentiate angiostatic steroids. It is likely that future investigations will uncover even more fundamental regulatory roles for heparin as well as for other polysaccharides in the normal function of growth factors, especially in the complex process of angiogenesis.

[1]  N. Ferrara,et al.  Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. , 1989, Biochemical and biophysical research communications.

[2]  K. Inoue,et al.  The sulfated polysaccharide-peptidoglycan complex potently inhibits embryonic angiogenesis and tumor growth in the presence of cortisone acetate. , 1988, Carbohydrate research.

[3]  M. Petitou,et al.  Binding and endocytosis of heparin by human endothelial cells in culture. , 1985, Biochimica et biophysica acta.

[4]  E. Levine,et al.  Human endothelial cells: use of heparin in cloning and long-term serial cultivation. , 1983, Science.

[5]  R. Hahnenberger,et al.  A simple method for shell-less cultivation of chick embryos. , 1989, Pharmacology & toxicology.

[6]  S. Szabó,et al.  Duodenal ulcer : discovery of a new mechanism and development of angiogenic therapy that accelerates healing , 1991 .

[7]  T. K. Hunt,et al.  Studies on inflammation and wound healing: angiogenesis and collagen synthesis stimulated in vivo by resident and activated wound macrophages. , 1984, Surgery.

[8]  J. Folkman,et al.  Mast cells and tumor angiogenesis , 1976, International journal of cancer.

[9]  J. Kenney,et al.  Interaction of endothelial cell growth factor with heparin: characterization by receptor and antibody recognition. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[10]  K. Inoue,et al.  The combination of a bacterial polysaccharide and tamoxifen inhibits angiogenesis and tumour growth. , 1991, International journal of radiation biology.

[11]  C W White,et al.  Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. , 1989, The New England journal of medicine.

[12]  D. Ingber,et al.  A heparin-binding angiogenic protein--basic fibroblast growth factor--is stored within basement membrane. , 1988, The American journal of pathology.

[13]  J. Folkman,et al.  Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. , 1984, Science.

[14]  M. Klagsbrun,et al.  Heparin affinity of anionic and cationic capillary endothelial cell growth factors: analysis of hypothalamus-derived growth factors and fibroblast growth factors. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[15]  K. Thomas,et al.  Purification and characterization of acidic fibroblast growth factor from bovine brain. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[16]  N. Ling,et al.  Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[17]  R. Thompson,et al.  Heparin-mediated release of fibroblast growth factor-like activity into the circulation of rabbits. , 1990, Growth factors.

[18]  S. Szabó,et al.  A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. , 1985, Science.

[19]  K. Inoue,et al.  Antitumor effects of an antiangiogenic polysaccharide from an Arthrobacter species with or without a steroid. , 1989, Cancer research.

[20]  R. Langer,et al.  Oral heparin results in the appearance of heparin fragments in the plasma of rats. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Y. Courtois,et al.  Bovine retina contains three growth factor activities with different affinity to heparin: eye derived growth factor I, II, III. , 1985, Biochimie.

[22]  G. Gray,et al.  Inhibition of tumor growth in mice by an analogue of platelet factor 4 that lacks affinity for heparin and retains potent angiostatic activity. , 1991, Cancer research.

[23]  R. Friesel,et al.  Heparin protects heparin-binding growth factor-I from proteolytic inactivation in vitro. , 1988, Biochemical and biophysical research communications.

[24]  J. Folkman,et al.  Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. , 1991, The New England journal of medicine.

[25]  Jeffrey D. Esko,et al.  Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor , 1991, Cell.

[26]  P. B. Weisz,et al.  Affinity of fibroblast growth factors for β-cyclodextrin tetradecasulfate , 1990 .

[27]  A. Schreiber,et al.  Heparin binds endothelial cell growth factor, the principal endothelial cell mitogen in bovine brain. , 1984, Science.

[28]  I. Leopold,et al.  Pharmacology and toxicology. , 1951, A.M.A. archives of ophthalmology.

[29]  E. Corey,et al.  Potentiation of angiostatic steroids by a synthetic inhibitor of arylsulfatase. , 1988, Laboratory investigation; a journal of technical methods and pathology.

[30]  J. Folkman,et al.  The role of heparin in angiogenesis. , 1983, Ciba Foundation symposium.

[31]  H. Nader,et al.  Heparin sequences in the heparan sulfate chains of an endothelial cell proteoglycan. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[32]  A. Tohgo,et al.  Inhibitory effects of heparin plus cortisone acetate on endothelial cell growth both in cultures and in tumor masses. , 1987, Journal of the National Cancer Institute.

[33]  M. Ruggiero,et al.  Internalization and metabolism of endogenous heparin by cultured endothelial cells. , 1986, Biochemical and biophysical research communications.

[34]  M. Klagsbrun,et al.  Purification and characterization of heparin-binding endothelial cell growth factors. , 1986, The Journal of biological chemistry.

[35]  J. Folkman,et al.  Importance of size, sulfation, and anticoagulant activity in the potentiation of acidic fibroblast growth factor by heparin. , 1989, The Journal of biological chemistry.

[36]  N. Bouck Tumor angiogenesis: the role of oncogenes and tumor suppressor genes. , 1990, Cancer cells.

[37]  N. Sakamoto,et al.  Effect of angiostatic steroid with or without glucocorticoid activity on metastasis. , 1987, Invasion & metastasis.

[38]  J. Glowacki,et al.  Mast cells in hemangiomas and vascular malformations. , 1982, Pediatrics.

[39]  J. Folkman,et al.  Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[40]  D. Rifkin,et al.  Membrane and matrix localization of proteinases: a common theme in tumor cell invasion and angiogenesis. , 1988, Biochimica et biophysica acta.

[41]  R. Koos,et al.  Factors That May Regulate the Growth and Regression of Blood Vessels in the Ovary , 1983 .

[42]  L. Dehner,et al.  TREATMENT OF HAEMANGIOENDOTHELIOMAS WITH ALPHA INTERFERON , 1989, The Lancet.

[43]  J. Folkman,et al.  Protamine is an inhibitor of angiogenesis , 1982, Nature.

[44]  J. Teissié,et al.  Basic fibroblast growth factor enters the nucleolus and stimulates the transcription of ribosomal genes in ABAE cells undergoing G0----G1 transition. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[45]  J. Folkman,et al.  Angiostatic steroids potentiated by sulfated cyclodextrins inhibit corneal neovascularization. , 1991, Investigative ophthalmology & visual science.

[46]  D. Rifkin,et al.  Endothelial cell-derived heparan sulfate binds basic fibroblast growth factor and protects it from proteolytic degradation , 1988, The Journal of cell biology.

[47]  S. Szabó Duodenal ulcer disease. Animal model: cysteamine-induced acute and chronic duodenal ulcer in the rat. , 1978, The American journal of pathology.

[48]  R. Sanderson,et al.  Syndecan, a developmentally regulated cell surface proteoglycan that binds extracellular matrix and growth factors. , 1990, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[49]  D. Moscatelli,et al.  Mr 25,000 heparin-binding protein from guinea pig brain is a high molecular weight form of basic fibroblast growth factor. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[50]  D. Gospodarowicz,et al.  Heparin protects basic and acidic FGF from inactivation , 1986, Journal of cellular physiology.

[51]  J. Folkman What is the evidence that tumors are angiogenesis dependent? , 1990, Journal of the National Cancer Institute.

[52]  L. Vrba,et al.  Inhibition of angiogenesis with combination treatments of angiostatic steroids and suramin. , 1991, International journal of radiation biology.

[53]  G. Mccormack Normal retinotopic mapping in human strabismus with anomalous retinal correspondence. , 1990, Investigative ophthalmology & visual science.

[54]  N. Fedarko,et al.  A unique heparan sulfate in the nuclei of hepatocytes: structural changes with the growth state of the cells , 1986, The Journal of cell biology.

[55]  G. Gray,et al.  Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides. , 1990, Science.

[56]  M. Maragoudakis,et al.  Antiangiogenic action of heparin plus cortisone is associated with decreased collagenous protein synthesis in the chick chorioallantoic membrane system. , 1989, The Journal of pharmacology and experimental therapeutics.

[57]  D. Ingber,et al.  Angiostatic steroids. Method of discovery and mechanism of action. , 1987, Annals of surgery.

[58]  C. Gajdusek Release of endothelial cell‐derived growth factor (ECDGAF) by heparin , 1984, Journal of cellular physiology.