The significance of hematogenous tumor cell clumps in the metastatic process

The relationship between the size distribution of vessels in an implanted tumor, the size distribution of tumor cell clumps collected in the venous effluent of the tumor, and the development of pulmonary metastases have been studied. The purpose is to evaluate the importance of clumps and their site of formation in the metastatic process. The results demonstrate a negative exponential character for both the size distribution of effluent tumor clumps and the tumor vessel population. Tumor trauma or massage increases total tumor cells and clumps released into the effluent. Serial amputation demonstrates that tumor cells are continuously being released on a day-by-day basis in vivo. A linear relationship exists between the proportion of vessels with diameters large enough to pass a tumor clump of a given size and the proportion of clumps of that size within the venous effluent. Injection of tumor cells in clumps of 6 to 7 cells produces a significantly greater number of metaststic foci than does a similar number of single tumor cells; larger clumps produce significantly more metastatic foci than do smaller clumps matched for the number of cells. These studies verify the significance of tumor clumps in the metastatic process. It is suggested that tumor cell clumps arise locally within the vascular bed of the tumor.