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Factors Affecting the Number of Tumor Metastases Experiments with a Transplantable Mouse Tumor^*

Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 4, Pa.)

Experiments were designed to determine the relationship between the number of embolic viable tumor cells and the number of resultant tumors. Serial dilutions of a suspension of viable cells from mouse Sarcoma 241 were injected into the tail veins of C57 mice. A direct proportionality was found between the number of cells injected and the number of tumors resulting in the lungs. It was also shown that very few tumors were formed in relation to the number of tumor cells injected, indicating a high mortality of the cells.

Further experiments were designed to determine the relationship of size and duration of growth of the primary tumor to the number of emboli released into the circulation. Using C57 mice with transplantable Sarcoma 241 it was found that:

1. The longer a primary tumor existed, the greater the number of emboli released, as judged by the number of metastases appearing in the lungs.

2. Mice inoculated with large tumor fragments had a greater number of metastatic tumors than did mice inoculated with smaller fragments.

3. There was not a significant correlation between the number of pulmonary metastases and the final size attained by the primary tumors.

It is concluded from these experiments:

1. That the number of metastases is directly proportional to the number of viable tumor cell emboli released into the circulation.

2. That although the number of emboli released may be affected by such simple factors as the initial size of the tumor inoculum and duration of growth of the primary tumors, it depends to an even greater extent upon factors within the primary tumor as yet unrecognized.

^* This investigation was supported by a research grant from the Division of Research Grants and Fellowships of the National Institutes of Health, U.S. Public Health Service.

Received 2/ 5/50.