Dying and regeneration of human tumor cells after heterotransplantation to athymic mice

The histologic phenomena occurring immediately after heterotransplantation of two human colon adenocarcinomas to athymic mice have been studied. The tumors differed with respect to velocity of growth and passage age. Three phases were discernible in both cases. (1) During the first phase, most inoculated tumor cells died. (2) The second phase was characterized by removal of the necrotic tumor cells by immigrated inflammatory cells and by penetration of the connective tissue of host animals from peripheral into central areas of the implants. The first mitoses occurred within tumor cells in close proximity to these connective tissue septa. (3) During the third phase, signs of regeneration and proliferation of tumor cells resulted in the macroscopic enlargement of xenografts. Only in this phase, the typical histologic characteristics of the tumors were formed. These observations point to the host connective tissue invading into implants to be of great importance for the stimulation of tumor cell proliferation and, therefore, for the growth of xenografts. Thus, successful heterotransplantation is obviously based on mutual events between the transplanted tumor cells and host connective tissue.