Procoagulant activity associated with plasma membrane vesicles shed by cultured tumor cells

Thirteen of 14 tumor cells or tumor cell lines of guinea pig, mouse, and human origin spontaneously shed procoagulant activity in short-term (4 or 14 to 22 hr) tissue culture under conditions of high cell viability. This released procoagulant activity was pelletable in the ultracentrifuge and was as...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1983-09, Vol.43 (9), p.4434-4442
Main Authors: DVORAK, H. F, VAN DEWATER, L, BITZER, A. M, ANDERSON, D, HARVEY, V. S, BACH, R, DAVIS, G. L, DEWOLF, W, CARVALHO, A. C. A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Blood Coagulation Factors - secretion
Cell Line
Cell Membrane - physiology
coagulation factors
Cysteine Endopeptidases
Endopeptidases - secretion
General aspects (metabolism, cell proliferation, established cell line...)
Guinea Pigs
Humans
Medical sciences
Mice
Neoplasm Proteins
Neoplasms - physiopathology
Neoplasms, Experimental - physiopathology
plasma membranes
Protein Precursors - secretion
Species Specificity
Tumor cell
tumor cell lines
Tumors
vesicles
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Summary:Thirteen of 14 tumor cells or tumor cell lines of guinea pig, mouse, and human origin spontaneously shed procoagulant activity in short-term (4 or 14 to 22 hr) tissue culture under conditions of high cell viability. This released procoagulant activity was pelletable in the ultracentrifuge and was associated with plasma membrane-derived vesicles as determined by transmission electron microscopy and marker enzyme analysis. The procoagulant activity shed corresponded to a substantial fraction of that expressed by intact or sonicated tumor cells and was composed of activities interacting at more than a single step in the clotting sequence. One procoagulant activity associated with shed human tumor vesicles behaved as tissue factor, requiring Factor VII for activity and being inhibited by a specific anti-bovine tissue factor antibody. Guinea pig tumor vesicles also exhibited tissue factor-like activity in a two-stage assay using homologous first-stage Factor VII/X concentrate. None of the human vesicles tested expressed a direct Factor X cleaving activity, independent of Factor VII. Shed tumor vesicles also acted at a second step late in the clotting cascade at the level of prothrombinase generation, presumably by providing a phospholipid surface. Taken together, these data indicate that a wide variety of tumor cells release plasma membrane vesicles with procoagulant activity. Such vesicles, as well as intact tumor cells themselves, may play an important role in the biology of tumor growth by inducing the local fibrin deposits found in association with many solid tumors.
ISSN:0008-5472
1538-7445