Activators of coagulation in cultured human lung-tumor cells.
Tumor matrix generation and tumor cell growth are supported by coagulation processes within the tumor tissue. Activators of coagulation were searched for in suspensions of 9 permanent human squamous-cell lung-cancer (EPLC 32MI, U1752), large-cell lung-cancer (LCLC 97TMI, LCLC 103H, U1810), and small-cell lung-cancer (N-592, H-526, DMS79, 86MI) cell lines. Incubation with these cells shortened the recalcification time in normal plasma (also in the presence of antibodies against tissue factor) or coagulation-factor-VII-, VIII-, IX- or X-deficient plasmas. The activators of coagulation in the 2 most active cell lines (U1752 and LCLC 103H) were further characterized in purified systems: the cleavage of chromogenic substrates, and the generation of markers of pro-thrombin activation were assessed. Three activators of coagulation were found in intact or sonicated cell suspensions and culture supernatants: (i) a tissue factor (TF)-like activity; (ii) an activity activating factor X, which in contrast to "cancer pro-coagulant" was not inhibited by iodoacetamide; and (iii) an activity-activating pro-thrombin, which was inhibited by the serine protease inhibitor PMSF and appeared to require plasmatic co-factor(s). The heterogeneous expression of coagulation activators by lung-tumor cell lines might be of significance for tumor biology and response to therapy.
Department of Internal Medicine, Philipps-University Hospitals, Marburg, Germany.
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R
Seitz
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Heidtmann
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M
Maasberg
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A
Immel
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Egbring
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Havemann
D001777:Blood Coagulation; D002118:Calcium / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood*; D018288:Carcinoma, Small Cell / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood*; D005170:Factor X / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000097:blood*; D011516:Prothrombin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D011516:Prothrombin; D005170:Factor X; D002118:Calcium