Studies correlating the growth rate of a tumor and its metastases and providing evidence for tumor-related systemic growth-retarding factors.

Abstract

Summary Previous studies have shown that the growth of a solid tumor is characterized by progressive slowing of the rate of growth as the tumor increases in size, but it is not clear to what extent local or systemic factors determine this slowing of growth rate. In this study, the growth of an implanted, isologous Lewis lung carcinoma in C57BL/6 mice was followed by serial tumor diameter measurements, and the number of tumor cells which had metastasized to lungs and kidneys was followed by serial quantitative transplant bioassay. Tumor diameter data were converted to tumor weight by a previously derived formula. Synchronous slowing of the rate of growth of the implanted tumor and its metastases was observed. Early after transplantation, the implanted tumor grew exponentially, and early lung metastases grew exponentially at a similar rate. Later, as the growth rate of the large implanted tumor slowed, a similar degree of slowing of the growth rate of metastases in lung and kidney was observed, even though these metastatic foci were microscopic in size. Host immunological factors did not seem to be involved, since challenge of animals at various stages of tumor growth with graded doses of tumor cells showed no evidence of transplantation resistance. Synchronous slowing of tumor growth rate was also demonstrated in experiments in which metastases were simulated by a 2nd implant. Following removal of the primary tumor, this slowing of tumor growth was reversible in both the lung metastases and the simulated metastases. These studies point to the importance of nonimmunological systemic factors (nutritional deficiencies or tumor by-products) that influence tumor growth rate.