VX2 carcinoma grown in rabbit thigh was minced and passed through sieves giving three approximate sizes of tumor particles: 495–246 µ, 246–38 µ, and 38 µ and less in diameter (large, medium, and small). Suspensions of particles were injected intravenously or into thigh muscle, and the lungs were studied in vivo and/or at autopsy with other organs. In vivo observations of lungs with VX2 growing in thigh indicated that most spontaneous metastases are clusters of cells (perhaps surrounded by precipitated material) 100–175 µ in diameter. Observations of lungs during intravenous (I.V.) injections showed that tumor particles caused acute embolic vascular responses similar to other pulmonary emboli.
Many of the small particles injected intravenously grew near the edge of the lung; others passed through the lungs and produced tumors, most frequently in liver and kidney, and less so in adrenal, brain, and spleen. Extrapulmonary growths from small particles were larger than pulmonary ones, and they grew faster. Spontaneous metastases and medium and large I.V. particles grew deeper within the lung, and tumors deep in the lung had a faster growth rate than those on the edge. I.V. VX2 particles grew from pulmonary arteries, arterioles, and capillaries, depending upon the size of the vessel embolized. In our opinion, the size of individual intravascular tumor particles is the primary and major determinant of their distribution. The particular vascular channels into which given particles pass are secondary determinants, and, in our opinion, transpulmonary passage of some small particles is a significant result of the interaction of these two factors within the lung.
In our opinion, the ideas contained in the “fertile soil” and “mechanical” hypotheses are not alternative or contradictory explanations of metastasis; rather, each emphasizes part of the sequence of time-dependent, interacting, necessary factors which determine where particles go, are arrested, and what happens after arrest.
Work supported in part by grants from the Durham-Orange County and American Heart Associations, the Life Insurance Medical Research Fund, and a research grant, H-1217, from the National Heart Institute, Public Health Service.