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

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Abstract
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 anti-genic 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.