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Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation

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Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation. / Stack, M S; Gately, S; Bafetti, L M; Enghild, J J; Soff, G A.

In: Biochemical Journal, Vol. 340 ( Pt 1), 1999, p. 77-84.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Stack, MS, Gately, S, Bafetti, LM, Enghild, JJ & Soff, GA 1999, 'Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation', Biochemical Journal, vol. 340 ( Pt 1), pp. 77-84.

APA

Stack, M. S., Gately, S., Bafetti, L. M., Enghild, J. J., & Soff, G. A. (1999). Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation. Biochemical Journal, 340 ( Pt 1), 77-84.

CBE

Stack MS, Gately S, Bafetti LM, Enghild JJ, Soff GA. 1999. Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation. Biochemical Journal. 340 ( Pt 1):77-84.

MLA

Vancouver

Stack MS, Gately S, Bafetti LM, Enghild JJ, Soff GA. Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation. Biochemical Journal. 1999;340 ( Pt 1):77-84.

Author

Stack, M S ; Gately, S ; Bafetti, L M ; Enghild, J J ; Soff, G A. / Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation. In: Biochemical Journal. 1999 ; Vol. 340 ( Pt 1). pp. 77-84.

Bibtex

@article{6afa53d0865711dda5a8000ea68e967b,
title = "Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation",
abstract = "Angiostatin, a kringle-containing fragment of plasminogen, is a potent inhibitor of angiogenesis. The mechanism(s) responsible for the anti-angiogenic properties of angiostatin are unknown. We now report that human angiostatin blocks plasmin(ogen)-enhanced in vitro invasion of tissue plasminogen activator (t-PA)-producing endothelial and melanoma cells. Kinetic analyses demonstrated that angiostatin functions as a non-competitive inhibitor of extracellular-matrix (ECM)-enhanced, t-PA-catalysed plasminogen activation, with a Ki of 0.9+/-0.03 microM. This mechanism suggests that t-PA has a binding site for the inhibitor angiostatin, as well as for its substrate plasminogen that, when occupied, prevents ternary complex formation between t-PA, plasminogen and matrix protein. Direct binding experiments confirmed that angiostatin bound to t-PA with an apparent Kd [Kd(app)] of 6.7+/-0.7 nM, but did not bind with high affinity to ECM proteins. Together, these data suggest that angiostatin in the cellular micro-environment can inhibit matrix-enhanced plasminogen activation, resulting in reduced invasive activity, and suggest a biochemical mechanism whereby angiostatin-mediated regulation of plasmin formation could influence cellular migration and invasion.",
keywords = "Angiostatins, Animals, Antibodies, Antiplasmin, Cattle, Cell Movement, Cells, Cultured, Endothelium, Vascular, Enzyme Activation, Extracellular Matrix, Extracellular Matrix Proteins, Female, Humans, Kinetics, Melanoma, Mice, Neovascularization, Pathologic, Peptide Fragments, Plasmin, Plasminogen, Protein Binding, Tissue Plasminogen Activator, Tumor Cells, Cultured",
author = "Stack, {M S} and S Gately and Bafetti, {L M} and Enghild, {J J} and Soff, {G A}",
year = "1999",
language = "English",
volume = "340 ( Pt 1)",
pages = "77--84",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",

}

RIS

TY - JOUR

T1 - Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation

AU - Stack, M S

AU - Gately, S

AU - Bafetti, L M

AU - Enghild, J J

AU - Soff, G A

PY - 1999

Y1 - 1999

N2 - Angiostatin, a kringle-containing fragment of plasminogen, is a potent inhibitor of angiogenesis. The mechanism(s) responsible for the anti-angiogenic properties of angiostatin are unknown. We now report that human angiostatin blocks plasmin(ogen)-enhanced in vitro invasion of tissue plasminogen activator (t-PA)-producing endothelial and melanoma cells. Kinetic analyses demonstrated that angiostatin functions as a non-competitive inhibitor of extracellular-matrix (ECM)-enhanced, t-PA-catalysed plasminogen activation, with a Ki of 0.9+/-0.03 microM. This mechanism suggests that t-PA has a binding site for the inhibitor angiostatin, as well as for its substrate plasminogen that, when occupied, prevents ternary complex formation between t-PA, plasminogen and matrix protein. Direct binding experiments confirmed that angiostatin bound to t-PA with an apparent Kd [Kd(app)] of 6.7+/-0.7 nM, but did not bind with high affinity to ECM proteins. Together, these data suggest that angiostatin in the cellular micro-environment can inhibit matrix-enhanced plasminogen activation, resulting in reduced invasive activity, and suggest a biochemical mechanism whereby angiostatin-mediated regulation of plasmin formation could influence cellular migration and invasion.

AB - Angiostatin, a kringle-containing fragment of plasminogen, is a potent inhibitor of angiogenesis. The mechanism(s) responsible for the anti-angiogenic properties of angiostatin are unknown. We now report that human angiostatin blocks plasmin(ogen)-enhanced in vitro invasion of tissue plasminogen activator (t-PA)-producing endothelial and melanoma cells. Kinetic analyses demonstrated that angiostatin functions as a non-competitive inhibitor of extracellular-matrix (ECM)-enhanced, t-PA-catalysed plasminogen activation, with a Ki of 0.9+/-0.03 microM. This mechanism suggests that t-PA has a binding site for the inhibitor angiostatin, as well as for its substrate plasminogen that, when occupied, prevents ternary complex formation between t-PA, plasminogen and matrix protein. Direct binding experiments confirmed that angiostatin bound to t-PA with an apparent Kd [Kd(app)] of 6.7+/-0.7 nM, but did not bind with high affinity to ECM proteins. Together, these data suggest that angiostatin in the cellular micro-environment can inhibit matrix-enhanced plasminogen activation, resulting in reduced invasive activity, and suggest a biochemical mechanism whereby angiostatin-mediated regulation of plasmin formation could influence cellular migration and invasion.

KW - Angiostatins

KW - Animals

KW - Antibodies

KW - Antiplasmin

KW - Cattle

KW - Cell Movement

KW - Cells, Cultured

KW - Endothelium, Vascular

KW - Enzyme Activation

KW - Extracellular Matrix

KW - Extracellular Matrix Proteins

KW - Female

KW - Humans

KW - Kinetics

KW - Melanoma

KW - Mice

KW - Neovascularization, Pathologic

KW - Peptide Fragments

KW - Plasmin

KW - Plasminogen

KW - Protein Binding

KW - Tissue Plasminogen Activator

KW - Tumor Cells, Cultured

M3 - Journal article

C2 - 10229661

VL - 340 ( Pt 1)

SP - 77

EP - 84

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

ER -