Human tumor spontaneous metastasis in immunosuppressed newborn rats. I. Characterization of the bioassay.

We characterize a new model of spontaneous metastasis of human tumor cells using anti-thymocyte serum (ATS) immunosuppressed newborn rats. We analyzed the intrinsic value of the bioassay of measurement of tumorigenicity and metastatic capacity using 17 human tumor cell lines, of which were 9 human malignant melanomas. Most of these cell lines revealed as tumorigenic and metastatic in lungs and/or lymph nodes 3 weeks after s.c. injection in the ventral flank of newborn rats, irrespective of their origin. All the melanoma cell lines that we injected were tumorigenic and 77% were metastatic, whereas the same cell lines grafted in nude mice showed no evidence of metastases after 6 weeks' examination. We were not able to show any relationship between tumorigenicity in nude mice and the malignant behavior of these cells in ATS-treated newborn rats. Likewise, neither chromosome abnormalities, nor antigenic marker expression were found to be related to tumor growth in nude mice or newborn rats. Two intrinsic parameters of the model were studied: number of cells injected vs. dose of ATS injected for one melanoma cell line; and role of the 3rd and 4th injections of ATS in the establishment and development of pulmonary metastases. Moreover, we show that s.c. injection in the ATS-treated newborn rat may represent a suitable method for studying melanoma cell tumor growth and spontaneous dissemination.