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Blood Coagulation Changes in Mice Bearing Lewis Lung Carcinoma, a Metastasizing Tumor¹

Istituto di Ricerche Farmacologiche "Mario Negri," Via Eritres, 62-20157 Milano, Italy

In view of the possible role of platelets and coagulation mechanisms in the growth and dissemination of solid tumors, a number of hematological parameters were followed during development of an experimental syngeneic tumor in mice, Lewis lung carcinoma. This tumor, when transplanted i.m. in C57BL/6 mice, grows locally and spontaneously metastasizes to the lungs. The transplanted animals survive for about 4 weeks. Metastases are visible from the third week. A slight but constant increase in plasma fibrinogen level and marked thrombocytopenia were first observed during the second week after tumor implantation. No other significant changes in coagulation and fibrinolysis parameters were detected. Moreover, the animals developed marked hemolytic anemia, possibly microangiopathic in origin, ¹²⁵I-labeled fibrinogen survival was decreased by about 20% during the second week after tumor implantation and was not further reduced later. Fibrinogen turnover was progressively accelerated, being more than doubled by the end of the third week. Labeled fibrinogen accumulated in the primary tumor and in the lungs (its rate of disappearance from the tumor was much slower than that from lungs or blood). ⁵¹Cr-labeled platelet survival did not change throughout the observation period, whereas platelet turnover was markedly reduced from the end of the second week, suggesting defective platelet production. ⁵¹Cr-labeled RBC survival was drastically reduced to about 30% of the controls starting from the second week.

The occurrence of low-grade, localized intravascular coagulation could be suggested on the basis of these data. Moreover, when Lewis lung carcinoma cells were abruptly injected i.v. through the tail vein, more impressive signs of intravascular coagulation could be seen. Indeed, there was a rapid decrease in the number of platelets, a reduction in fibrinogen, and an increase in fibrin-fibrinogen degradation products. The effects of i.v. injection of Lewis lung carcinoma cells indicate a relevant interference of cancer cells with the hemostatic system. In contrast, the tenuous evidence for coagulation disorders in animals receiving injections of tumor cells i.m. seems to indicate a limited effect on hemostasis of the same cells during i.m. tumor growth.

¹ This is Paper 1 of a series on Cancer and Hemostasis. Supported by Grants NIH PHRB-1 RO1, CA 12764-01, and CNR (Italian Research Council) 73.00400.04. Part of this work was presented at the 11th International Cancer Congress, Florence, Italy, October 1974. Also, a portion of the research aimed at defining the anemia developing in 3LL-bearing mice was performed at the Department of Hematology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.

² Recipient of a Wellcome Italian Research travel grant. To whom requests for reprints should be addressed.

Received 12/30/75. Accepted 6/14/76.