Metastases of human tumor xenografts in nude mice.

In the present study, using systematic microscopic examination, we tried to determine the true incidence of metastases in nude mice bearing a wide variety of human tumors. A total of 63 malignant tumors were successfully transplanted subcutaneously and 831 nude mice bearing tumors were examined. It appeared that 17 of the 63 tumors (26.9%) retained their metastatic ability in nude mice. Most of these tumors were adenocarcinomas (11/17 cases). Generally the metastatic deposits in the lungs and, to a lesser extent, in the lymph nodes were small and thus only detectable on microscopic examination. We also found a positive correlation between the presence of metastases and neoplastic infiltration of the lymphatic and/or blood vessels around the subcutaneous tumors. Metastatic human tumors, including neoplastic cells from effusion, exhibited higher metastatic ability than primary tumors (p less than 0.005). However, the expression of this metastatic potential depends on several factors including tumor volume, survival time after inoculation and murine hepatitis infection. Thus, animals with metastases bore larger tumors (9.56 cm3) than those without metastasis (6.35 cm3; p less than 0.0001). Moreover, survival time after inoculation was longer in mice with metastases (104 days) than in mice without metastases (81 days; p less than 0.0001). A negative influence of viral hepatitis on the incidence of metastases was observed. This may simply be related to the shortened life span of the animals. Death due to this infection may precede the expression of the metastatic potential.