Development of an orthotopic transplantation model in nude mice that simulates the clinical features of human lung cancer.

The objective of the present study was to establish an orthotopic tumor transplantation model in nude mice that closely resembles the clinical features of human lung cancer. The human lung adenocarcinoma A549 cell line and the squamous cell carcinoma SQ5 cell line were used. Tumor cells suspended in serum-free medium were injected directly into the main bronchi of anesthetized female Balb/c athymic nude mice (7-9 weeks old) with or without simultaneous administration of 0.01 M ethylenediaminetetracetic acid (EDTA). In some experiments, lung carcinoma cells harvested from tumors transplanted subcutaneously were recultured and used for intratracheal implantation. Tumor nodules that formed in the lung were counted and confirmed by histological examination. Administration of A549 cells with EDTA resulted in a 70% engraftment rate (n = 10). Recultured A549 cells without and with EDTA resulted in 20% (n = 5) and 80% (n = 5) engraftment rates, respectively. Administration of SQ5 cells without or with EDTA formed 50% (n = 4) and 67% (n = 6) engraftment rates, respectively. Recultured SQ5 cells with EDTA further increased the engraftment rate to 100% (n = 6). Multiple tumors formed mainly in the left lung and the upper lobe of the right lung. Simultaneous administration of EDTA resulted in greater numbers of tumor nodules in the lung. Histological findings revealed that A549 tumor nodules were distributed primarily in alveoli. The SQ5 solid tumors invaded bronchioles and occupied the alveoli. This reproducible orthotopic transplantation model produced tumor growth that simulated the clinical features of human lung cancer.