Rofstad E K
Department of Biophysics, Norwegian Radium Hospital, Montebello, Oslo, Norway.
Int J Cancer. 1995 Nov 27;63(5):744-9. doi: 10.1002/ijc.2910630523.
Congenitally athymic nude (nu/nu) mice have been used extensively as hosts to study the metastatic properties of xenografted human tumors. It has not been fully explored to what extent the metastatic behavior of human tumor xenografts reflects the intrinsic properties of the tumor cells and to what extent it is influenced artificially by the host. The purpose of the work reported here was to evaluate the potential usefullness of athymic mice for qualitative and quantitative assessment of the intrinsic metastatic properties of human tumor cells. Four human melanoma cell lines (A-07, D-12, R-18, U-25) were included in the study. Quantitative intradermal and intracranial transplantation assays were used to determine the tumorigenicity and immunogenicity of the cell lines. The metastatic behavior of the cell lines was studied by inoculating cells intra-arterially or intravenously (artificial metastases) or intradermally (spontaneous metastases). The influence of the host on the incidence of metastases was assessed by inoculating cells intravenously in immunologically modified athymic mice. Both the intradermal and intracranial tumorigenicity differed substantially between the cell lines. The host immune reactivity against heterotransplantation was significantly lower for D-12 than for A-07, R-18 and U-25 cells. The incidence of metastases was influenced significantly by the host immune reactivity. The cell lines showed organ-specific metastatic patterns in athymic mice. The organs of preference were lungs for A-07 and D-12 cells, lymph nodes for R-18 cells, and brain for U-25 cells. The organ-specific metastatic pattern in athymic mice reflected the pattern of distant metastases in the donor patients. In addition, all cell lines gave rise to metastases in abdominal organ sites, but without organ specificity. The incidence of abdominal metastases was influenced significantly by the tumorigenicity of the cell lines. In conclusion, athymic mice appear to be excellent hosts for assessment of the organ specificity in the metastatic behavior of human tumors. The metastasis frequency of human tumors in athymic mice, however, might be a misleading quantitative measure of the intrinsic metastatic propensity of the tumor cells, owing to the cell-line-dependent host immune reactivity.
先天性无胸腺裸鼠（nu/nu）已被广泛用作宿主，以研究异种移植人类肿瘤的转移特性。人类肿瘤异种移植的转移行为在多大程度上反映肿瘤细胞的内在特性，以及在多大程度上受到宿主的人为影响，目前尚未得到充分探索。本文报道的这项工作的目的是评估无胸腺小鼠在定性和定量评估人类肿瘤细胞内在转移特性方面的潜在用途。该研究纳入了四种人类黑色素瘤细胞系（A - 07、D - 12、R - 18、U - 25）。采用定量皮内和颅内移植试验来确定细胞系的致瘤性和免疫原性。通过动脉内或静脉内接种细胞（人工转移）或皮内接种细胞（自发转移）来研究细胞系的转移行为。通过在免疫修饰的无胸腺小鼠中静脉内接种细胞，评估宿主对转移发生率的影响。各细胞系的皮内和颅内致瘤性存在显著差异。D - 12细胞相对于A - 07、R - 18和U - 25细胞，宿主对异种移植的免疫反应性显著更低。转移发生率受到宿主免疫反应性的显著影响。这些细胞系在无胸腺小鼠中表现出器官特异性转移模式。A - 07和D - 12细胞倾向于转移至肺部，R - 18细胞倾向于转移至淋巴结，U - 25细胞倾向于转移至脑部。无胸腺小鼠中的器官特异性转移模式反映了供体患者远处转移的模式。此外，所有细胞系都在腹部器官部位发生转移，但无器官特异性。腹部转移的发生率受到细胞系致瘤性的显著影响。总之，无胸腺小鼠似乎是评估人类肿瘤转移行为中器官特异性的优良宿主。然而，由于宿主免疫反应性依赖于细胞系，无胸腺小鼠中人类肿瘤的转移频率可能是肿瘤细胞内在转移倾向的误导性定量指标。
