thromboxane-b2 and Fibrosarcoma

We investigated whether there is a relationship between the production of eicosanoids by murine solid tumors and their response to the prostaglandin H (PGH) synthase inhibitor indomethacin. Three sarcomas, designated FSA, NFSA, and SA-NH, and two carcinomas, designated MCA-K and HCA-I, syngeneic to C3Hf/Kam mice were used. In general, FSA and NFSA produced more PGH synthase products than lipoxygenase products, whereas HCA-I produced both types of metabolites in large quantities. All three tumors responded well to indomethacin treatment by slowing their growth. In contrast, MCA-K and SA-NH tumors produced insignificant quantities of PGH synthase products, but substantial amounts of lipoxygenase products. Their growth was not affected by treatment with indomethacin. Indomethacin did not influence tumor cell survival either in vitro or in vivo, but it reduced the proportion of S-phase cells in the tumors. The antitumor effect of indomethacin was not reduced by immunosuppression of the tumor host and was independent of tumor immunogenicity, implying that indomethacin acted through nonimmunological mechanisms. Thus, the effectiveness of indomethacin was directly related to the ability of tumors to produce PGs. Consequently, the eicosanoid profile of tumors could serve as a valuable way to select patients likely to respond to indomethacin and other PGH synthase inhibiting agents.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Biomarkers, Tumor; Carbon Radioisotopes; Female; Fibrosarcoma; Indomethacin; Liver Neoplasms, Experimental; Male; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H; Prognosis; Prostaglandins; Sarcoma, Experimental; Thromboxane B2; Tritium

Growth of BN175, a malignant fibrosarcoma, was correlated with high plasma TXB2 and PGE2 levels. This statistically significant increase was first detected 17 days after inoculation of the tumor, at which time the tumors were 20 mms in diameter. A further increase in tumor size was associated with still higher PGE2 and TXB2 values. At the same time, progressive alterations in platelet function, as measured by ADP-induced platelet aggregation, were observed. 6-keto-PGF1 alpha levels remained normal throughout the whole experiment. It was concluded that tumor growth was associated with changes in PG synthesis and platelet function, although it remains unclear whether these changes were caused by some host immunological response towards the tumor or were predominantly the result of tumor PG-synthesis.

Topics: Animals; Culture Techniques; Dinoprostone; Female; Fibrosarcoma; Gamma Rays; Neoplasm Metastasis; Neoplasm Transplantation; Platelet Aggregation; Prostaglandins; Prostaglandins E; Rats; Thromboxane B2

In a previous study we found a correlation between metastatic potential and platelet aggregating activity in sublines of a benzopyrene-induced murine fibrosarcoma ( mFS6 ); the purpose of the present work was to elucidate the role of thromboxane biosynthesis by platelets and/or by neoplastic cells in the activation of platelets in this system. The cells of the more malignant subline induced higher aggregation and TxB2 production than those of the non metastasizing one. The supernatants of aggregating cell suspensions contained very few TxB2; furthermore, preincubation of platelets with ASA or Apyrase resulted in inhibition of aggregation and TxB2 production, while preincubation of the cells was ineffective; these results suggest the platelet origin of the measured TxB2 and indicate that platelet-derived ADP plays an important role in their activation, while the production of ADP by the cells does not seem to be relevant in this model. The involvement of platelet prostaglandin biosynthesis pathway in neoplastic cell induced platelet activation could play an important role in the development of platelet-dependent tumour metastasis.

Topics: Animals; Apyrase; Aspirin; Blood Platelets; Cell Line; Cell Transformation, Neoplastic; Fibrosarcoma; Humans; Mice; Platelet Aggregation; Thromboxane B2; Thromboxanes