Isolation of subclones with different tumorigenicity and metastatic ability from rat nephroblastoma cell line, ENUT

Seven subclones derived from a chemically induced rat nephroblastoma cell line, ENUT, were isolated and their cytological characteristics were examined in order to investigate the biological nature of the parent tumor. The subclones were divisible into two types based on morphological and biological features: polygonal cells with well developed junctional complexes and less developed cell surface microvilli, showing a doubling time of 13.0 to 14.0 h and tumorigenicity in nude mice of 42-100%, and spindle-shaped cells with poorly developed junctional complexes and well developed microvilli, showing a doubling time of 9.7 to 12.2 h and 100% tumorigenicity. Potential for both spontaneous and experimental metastasis to the lungs was apparently higher in the spindle-shaped clones than in the polygonal clones. In spite of their differing characteristics, the cytochemical phenotypes of the two clonal types were almost identical to those of immature renal tubules of the developing fetal kidney. The present findings suggest that these subclones possess characteristics of early nephrogenic epithelial cells, and we speculate that the biological differences observed among the subclones may be explained by differences in malignant progression. In addition, these clones appear to be a useful model for the study of tumorigenicity and metastasis.