[A study on the augmentation of experimental tumor metastasis in mice with granulocytosis]

Abstract

When a methylcholanthrene-induced fibrosarcoma, BMT-11, and its eight clones were transplanted subcutaneously into syngeneic C57BL/6 mice, leukemoid reaction characterized by a progressive increase in peripheral white blood cells (WBC) and splenomegaly was observed as the tumors grew. The WBC count reached about 40-fold of normal level and more than 90% of them were found to be polymorphonuclear leukocytes (PMN). The increase in WBC was correlated with tumor size and its count decreased to normal level within 7 days after surgical excision of subcutaneous tumors. Moreover, a high level of colony-stimulating-factor was detected in the supernatant of BMT-11 culture. I have exploited such "granulocytosis-positive" mice to examine the influence of PMN on the metastatic colonization of tumor cells. The number of B16 melanoma lung colonies detected after intravenous (i.v.) injection was significantly higher in BMT-11 tumor-bearing mice with granulocytosis than in control mice. Retention of 125IUdR-labeled B16 cells 24 hr after the i.v. injection was 3 to 10 times greater in mice with granulocytosis than in controls. Either simultaneous injection, or preinjection of PMN with B16 cells, increased the lung-colonizing capacity of B16 melanoma cells. These results suggest that abnormally increased numbers of PMN in the peripheral blood can enhance the ability of tumor cells to metastasize.