Induction of Metastasis of Frog Carcinoma by Increase of Environmental Temperature

Metastasis of the kidney carcinoma of leopard frogs (Rana pipiens) has been induced by exposing tumor-bearing animals for approximately 50 days to a constant temperature of 28 degrees C. Under these conditions 54 per cent of the frogs developed secondary growths, whereas in groups kept at 18 degrees or at 7 degrees metastatic dissemination was found in only 6 per cent. Moreover, at the elevated temperature the metastases were usually more numerous and more widely disseminated; they were also fairly uniform in size, suggesting that they had developed at nearly the same time. Dissemination of the kidney tumors was influenced by the nutritional state of the frogs, occurring more readily in well nourished than in poorly nourished animals. Periodic Roentgen ray examinations showed that the size of the primary tumors was not significantly or uniformly affected during the course of the experiments. No correlation was found between change in size of the kidney tumors and the incidence of their metastasis. Although the mechanism by which temperature induces metastasis of frog carcinoma cannot as yet be elucidated, previous experiments with this tumor indicate that certain factors at least may be involved: Elevation of temperature has been found to cause more ready detachment of cells of frog carcinoma in tissue culture; to bring about increased velocity of locomotion of the detached cells; to lead more promptly and efficiently to vascularization of transplants; and to effect their greater invasiveness.