Activators of coagulation in cultured human lung‐tumor cells

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Abstract
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, U 1810), 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.