'Endostatin is a potent endogenous angiogenesis inhibitor that induces regression of tumors in mice. Neither an extracellular receptor for endostatin nor intracellular signals that result in the regression of tumor vascular beds have been identified. We demonstrate that endostatin, but not angiostatin, at comparable concentrations to those used in in ... More
Solution conformation of a synthetic fragment of human pituitary growth hormone. Two-dimensional NMR of an alpha-helical dimer.
AuthorsRoongta V, Powers R, Jones C, Beakage MJ, Shields JE, Gorenstein DG
JournalBiochemistry
PubMed ID2713357
'Circular dichroism and two-dimensional NMR spectra indicate that a peptide fragment consisting of the first 28 residues from the N-terminus of human growth hormone (hGH 1-28) has considerable alpha-helical structure. The peptide, (1) H-Phe-Pro-Thr-Ile-Pro-Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala-Met-Leu-Arg-Ala-Hi s-Arg- Leu-His-Gln-Leu-Ala-Phe-Asp-Thr-Tyr-OH (28), was synthesized on an automated peptide synthesizer using the Merrifield solid-phase method. The ... More
Angiostatin and angiostatin-related proteins.
AuthorsSoff GA
JournalCancer Metastasis Rev
PubMed ID11191071
'The study of angiogenesis, and the promise of angiogenesis inhibition as a means of cancer therapy, has dramatically accelerated in the last several years. The discovery and publication of angiostatin by O''Reilly and colleagues in Judah Folkman''s lab in 1994 has greatly contributed to this progress. Angiostatin is a kringle-containing ... More
Angiostatin effects on endothelial cells mediated by ceramide and RhoA.
AuthorsGupta N, Nodzenski E, Khodarev NN, Yu J, Khorasani L, Beckett MA, Kufe DW, Weichselbaum RR
JournalEMBO Rep
PubMed ID11415988
'Angiostatin is a cleavage product of plasminogen that has anti-angiogenic properties. We investigated whether the effects of angiostatin on endothelial cells are mediated by ceramide, a lipid implicated in endothelial cell signaling. Our results demonstrate that angiostatin produces a transient increase in ceramide that correlates with actin stress fiber reorganization, ... More
Angiogenesis in cancer, vascular, rheumatoid and other disease.
AuthorsFolkman J
JournalNat Med
PubMed ID7584949
Recent discoveries of endogenous negative regulators of angiogenesis, thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor, all associated with neovascularized tumours, suggest a new paradigm of tumorigenesis. It is now helpful to think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood ... More
Liposome-delivered angiostatin strongly inhibits tumor growth and metastatization in a transgenic model of spontaneous breast cancer.
AuthorsSacco MG, Caniatti M, Catò EM, Frattini A, Chiesa G, Ceruti R, Adorni F, Zecca L, Scanziani E, Vezzoni P
JournalCancer Res
PubMed ID10825138
The possibility to inhibit tumor growth by interfering with the formation of new vessels, which most neoplasias depend on, has recently raised considerable interest. An angiogenic switch, in which proliferating cells acquire the ability to direct new vessel formation, is thought to be an early step in the natural history ... More
A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer.
AuthorsSim BK, O'Reilly MS, Liang H, Fortier AH, He W, Madsen JW, Lapcevich R, Nacy CA
JournalCancer Res
PubMed ID9102221
Endogenous murine angiostatin, identified as an internal fragment of plasminogen, blocks neovascularization and growth of experimental primary and metastatic tumors in vivo. A recombinant protein comprising kringles 1-4 of human plasminogen (amino acids 93-470) expressed in Pichia pastoris had physical properties (molecular size, binding to lysine, reactivity with antibody to ... More
The tumor-suppressing activity of angiostatin protein resides within kringles 1 to 3.
AuthorsMacDonald NJ, Murad AC, Fogler WE, Lu Y, Sim BK
JournalBiochem Biophys Res Commun
PubMed ID10529387
Angiostatin protein, which comprises the first four kringle domains of plasminogen, is an endogenous inhibitor of angiogenesis that inhibits the growth of experimental primary and metastatic tumors. Truncation of Angiostatin K1-4 to K1-3 retained the activity of Angiostatin. We recombinantly expressed full-length human Angiostatin protein corresponding to the first four ... More
Plasmin-induced migration of endothelial cells. A potential target for the anti-angiogenic action of angiostatin.
AuthorsTarui T, Majumdar M, Miles LA, Ruf W, Takada Y
JournalJ Biol Chem
PubMed ID12087108
Angiostatin, a plasminogen fragment containing 3-4 N-terminal kringle domains, is a potent inhibitor of tumor-induced angiogenesis, but its mechanism of action is unclear. Angiostatin is a ligand for integrin alphavbeta(3) but does not induce stress fiber formation upon integrin binding, suggesting that angiostatin is a potential integrin antagonist. Plasmin, the ... More
Human glioma cell BT325 expresses a proteinase that converts human plasminogen to kringle 1-5-containing fragments.
AuthorsLi F, Yang J, Liu X, He P, Ji S, Wang J, Han J, Chen N, Yao L
JournalBiochem Biophys Res Commun
PubMed ID11095991
Angiostatin, a specific angiogenesis inhibitor, is an internal fragment of plasminogen, and can be generated in many systems mediated by different enzymes in vitro. The mechanism of angiostatin generation in vivo has not been well defined. Here we demonstrated that human glioma cell line BT325 can express an enzyme that ... More
Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation.
AuthorsGriffioen AW, Molema G
JournalPharmacol Rev
PubMed ID10835101
Angiogenesis, or the formation of new blood vessels out of pre-existing capillaries, is a sequence of events that is fundamental to many physiologic and pathologic processes such as cancer, ischemic diseases, and chronic inflammation. With the identification of several proangiogenic molecules such as the vascular endothelial cell growth factor, the ... More
The mechanism of cancer-mediated conversion of plasminogen to the angiogenesis inhibitor angiostatin.
AuthorsGately 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
JournalProc Natl Acad Sci U S A
PubMed ID9380726
Angiostatin, a potent naturally occurring inhibitor of angiogenesis and growth of tumor metastases, is generated by cancer-mediated proteolysis of plasminogen. Human prostate carcinoma cells (PC-3) release enzymatic activity that converts plasminogen to angiostatin. We have now identified two components released by PC-3 cells, urokinase (uPA) and free sulfhydryl donors (FSDs), ... More
Specific interaction of angiostatin with integrin alpha(v)beta(3) in endothelial cells.
AuthorsTarui T, Miles LA, Takada Y
JournalJ Biol Chem
PubMed ID11514539
Angiostatin, the N-terminal four kringles (K1-4) of plasminogen, blocks tumor-mediated angiogenesis and has great therapeutic potential. However, angiostatin's mechanism of anti-angiogenic action is unclear. We found that bovine arterial endothelial (BAE) cells adhere to angiostatin in an integrin-dependent manner and that integrins alpha(v)beta(3), alpha(9)beta(1), and to a lesser extent alpha(4)beta(1), ... More
Endogenous angiogenesis inhibitors and their therapeutic implications.
AuthorsCao Y
JournalInt J Biochem Cell Biol
PubMed ID11312106
A number of endogenous inhibitors targeting the tumor vasculature have recently been identified using in vitro and in vivo antiangiogenesis models. While many of these angiogenesis inhibitors display a broad spectrum of biological actions on several systems in the body, several inhibitors including angiostatin, endostatin, and serpin antithrombin seem to ... More