GROWTH OF A LOCAL TUMOR EXERTS A SPECIFIC INHIBITORY EFFECT ON PROGRESSION OF LUNG METASTASES

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Abstract
The effects of local tumor growth on the progression of lung metastasis of two mouse tumors of C57BL origin—the 3LL Lewis lung carcinoma and the B‐16 melanoma—were studied. Excision of primary footpad grafts of 3LL or B‐16 resulted in a significant increase in incidence and size of lung metastases. The incidence, but not the size, of lung metastases was found to be a function of size of the local tumor at time of excision. Reinoculation of tumor cells in the left footpad following excision of tumor from the right footpad suppressed the acceleration of growth of lung metastases and their increased incidence. Thus, the progression of the local tumor exerts an inhibitory effect on lung metastasis. The extent of inhibition of accelerated metastatic development by reinoculated tumor cells is a function of size of the cell inoculum or, in fact, of mass of the local tumor. The inhibitory effect of the local tumor on lung metastasis seems to be tumor‐specific. 3LL metastases were not inhibited by local B‐16 or EL4, neither was B‐16 metastasis inhibited by 3LL. The specificity of interactions between the local tumor growth and its metastases may suggest the participation of immunological mechanisms in the control of lung metastasis. The involvement of the lymphoid system in the control of metastatic progression is also supported by the observation that total‐body X‐irradiation was associated with an increase in lung metastasis and that splenomegaly was observed in mice bearing the footpad tumor. Its excision resulted in the prevention of splenomegaly but reinoculation of the tumor, leading to metastatic suppression, was again associated with splenomegaly.