A polypeptide factor produced by fibrosarcoma cells that induces endothelial tissue factor and enhances the procoagulant response to tumor necrosis factor/cachectin

Matthias Clauss, J. Clifford Murray, Maria Vianna, Rob De Waal, Gavin Thurston, Peter Nawroth, Herwig Gerlach, Marlene Gerlach, Ronald Bach, Philip C. Familletti, David Stern

Research output: Contribution to journalArticle

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Abstract

Intravascular clot formation, localized to the neoplasm, is an early component of the vascular response to tumor necrosis factor (TNF)/cachectin. Fibrin is closely associated with the endothelial cell surface, and multiple microthromboses lead to reduced blood flow in the tumor. We have identified a tumor-derived mediator which enhances endothelial procoagulant activity and the cellular response to TNF using cultured cells derived from a murine methylcholanthrene A (meth A)-induced fibrosarcoma as a model system. A heat-stable protease K-sensitive polypeptide, Mr ≈44,000 on nonreduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Mr ≈56,000 reduced), was purified ≈500,000-fold from serum-free culture supernatants of meth A cells by sequential Q-Sepharose, Mono S, reversed phase, and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Based on immunologic criteria, biologic activity, and other molecular properties, meth A factor appears to be distinct from other cytokines and growth factors. Purified meth A factor induced transcription of the tissue factor gene and expression of procoagulant activity by cultured human endothelium (half-maximal effect for the latter at ≈6-8 pM). Furthermore, coincubation of endothelium with meth A factor together with TNF enhanced induction of tissue factor in a more than additive manner. These data indicate that certain tumors elaborate an apparently unique molecule which can alter hemostatic properties of the vessel wall, potentially modulating reactivity of the tumor vasculature to host response mediators.

Original languageEnglish (US)
Pages (from-to)7078-7083
Number of pages6
JournalJournal of Biological Chemistry
Volume265
Issue number12
StatePublished - 1990
Externally publishedYes

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Methylcholanthrene
Fibrosarcoma
Thromboplastin
Endothelium
Tumor Necrosis Factor-alpha
Tumors
Peptides
Neoplasms
Electrophoresis
Sodium Dodecyl Sulfate
Polyacrylamide Gel Electrophoresis
Endopeptidase K
Endothelial cells
Hemostatics
Transcription
Fibrin
S Phase
Human Activities
Sepharose
Blood Vessels

ASJC Scopus subject areas

  • Biochemistry

Cite this

A polypeptide factor produced by fibrosarcoma cells that induces endothelial tissue factor and enhances the procoagulant response to tumor necrosis factor/cachectin. / Clauss, Matthias; Clifford Murray, J.; Vianna, Maria; De Waal, Rob; Thurston, Gavin; Nawroth, Peter; Gerlach, Herwig; Gerlach, Marlene; Bach, Ronald; Familletti, Philip C.; Stern, David.

In: Journal of Biological Chemistry, Vol. 265, No. 12, 1990, p. 7078-7083.

Research output: Contribution to journalArticle

Clauss, M, Clifford Murray, J, Vianna, M, De Waal, R, Thurston, G, Nawroth, P, Gerlach, H, Gerlach, M, Bach, R, Familletti, PC & Stern, D 1990, 'A polypeptide factor produced by fibrosarcoma cells that induces endothelial tissue factor and enhances the procoagulant response to tumor necrosis factor/cachectin', Journal of Biological Chemistry, vol. 265, no. 12, pp. 7078-7083.
Clauss, Matthias ; Clifford Murray, J. ; Vianna, Maria ; De Waal, Rob ; Thurston, Gavin ; Nawroth, Peter ; Gerlach, Herwig ; Gerlach, Marlene ; Bach, Ronald ; Familletti, Philip C. ; Stern, David. / A polypeptide factor produced by fibrosarcoma cells that induces endothelial tissue factor and enhances the procoagulant response to tumor necrosis factor/cachectin. In: Journal of Biological Chemistry. 1990 ; Vol. 265, No. 12. pp. 7078-7083.
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AU - Thurston, Gavin

AU - Nawroth, Peter

AU - Gerlach, Herwig

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