In Vivo Invasion Assay of Low Passage Cultured Cells Derived from Human Lung Cancer Using Deepithelialized Rat Tracheas Xenotransplanted into Nude Mice

Abstract

Human lung tumor-derived cell lines with low passage generation were transplanted into nude mice to determine their growth behavior and invasive potential. Six cell lines (HKT-2, HKT-3, HKT-5, HKT-6, HKT-7, HKT-8) were inoculated into deepithelialized rat trachea (5 × 10⁵ cells/trachea). After cell inoculation, the tracheas were sealed and transplanted into the subcutis of nude mice. In a parallel experiment, these cell lines (1 × 10⁶ cells) were injected s.c. In the subcutis, the tumor take rate of HKT-3, the lowest of all, was only 13% with a long latency period of 18 weeks, and 3 cell lines (HKT-2, HKT-3, HKT-7) did not show any invasive growth to the surrounding tissue. In rat tracheas, all cell lines proliferated within 3 weeks, and 4 of them (HKT-2, HKT-5, HKT-6, HKT-8) showed invasive growth to the tracheal wall within 1–2 weeks. Cells growing in the tracheal wall showed higher [³H]thymidine labeling indexes and greater atypia, such as larger nuclei and prominent nucleoli, than those in the tracheal lumen. The s.c. tumor take rate correlated with the incidence of invasive growth to the tracheal wall. The survival of the patients originally bearing the six tumors also correlated closely with the invasive potential of this system. These results indicate that the system using low passage cell lines can evaluate the invasive potential shortly after the inoculation of a relatively small number of cells and can be used as a clinically reliable biological invasion assay.