Heterotransplantation of Human Malignant Tumors in “Nude” Thymusless Mice. II. Malignant Tumors Induced by Injection of Cell Cultures Derived From Human Solid Tumors

Summary

Eleven cell lines derived in our laboratory from human malignant tumors (6 melanomas, 2 fibrosarcomas, 1 osteosarcoma, 1 malignant teratoma, 1 metastatic carcinoma of uncertain origin) were injected subcutaneously or lntradermally into pathogen-free “nude” thymusless mice at doses from 1×10⁵ to 2×10⁷ cells. Seven cell lines gave origin to 37 malignant tumors which reached large sizes if the mice were not killed earlier. Frequently, the abdominal cavity was invaded and internal organs were destroyed. Eleven animals were killed when moribund or died of their tumor. Three tumors metastasized to lymph nodes and 1 to the lungs. Of 37 human tumors in 26 nudes, only 3 spontaneously regressed and 1 of these host mice later developed a rapidly growing metastasis. All tumors in the nudes were cultured and karyotyped. All had a human karyotype. Five human lines derived from normal embryonary tissues were also injected into nude mice. None produced tumors, even when 1×10⁸ cells were injected and the animals followed for more than 4 months. To further study the capability of the nude to differentiate between normal and neoplastic cells, murine cell lines were injected. Three of 3 neoplastic lines (l.e., capable of inducing tumors in syngenic mice) produced malignant neoplasms. One (MEF IT) required an inoculum of only 1×10³ cells. MEF1 (a line not producing tumors in syngenic animals and growing in culture at the same rate of MEF IT) did not give origin to tumos even when 4×10⁸ cells were injected into the nudes and the animals followed for 6 months or more.