Development of a human to murine orthotopic xenotransplanted lung cancer model.

The goal was to develop a clinically relevant animal model that could be used to assess the efficacy of therapeutic interventions in lung cancer. Two cell lines, noncancerous control (BEAS2-B, immortalized human bronchial-epithelial cell line) and cancerous (BZR-T33, H-ras transformed BEAS2-B) were implanted into nude (athymic) mice. Two groups (n = 10 each) received dorsoscapular subcutaneous injection of 10(6) cells from either cell line. BEAS2-B cells were nontumorigenic, whereas mice with BZR-T33 cells had tumors (9,510 +/- 4,307 mm3) confirmed by histology, and a significantly smaller body weight (BZR-T33, 28.5 +/- 0.49 vs. BEAS2-B, 30.7 +/- 0.75 g, p < .05). The next phase evaluated invasion/metastasis. Two groups (n = 10 each) received 10(6) cells from either cell line injected into tail veins. Animals receiving BZR-T33 cells had a smaller body weight, palpable lung masses (67%), obvious tail masses (44%), and average tumor burden (1,120 +/- 115 mm3), and histology revealed invasion of lung tissue and interstitial hemorrhage. In development of the orthotopic xenotransplanted model, mice (2 groups, n = 10 each) received 10(6) cells from either cell line implanted into the lungs through a tracheotomy. Animals with BZR-T33 cells did not survive past 59 days and had a smaller body weight, increased lung weight, lung masses (100%), and metastatic loci (30%). Magnetic resonance imaging (MRI) confirmed the presence of masses in intubated live mice, later confirmed by histology. In summary, the H-ras transfected cell line developed lung masses following tail-vein injection and endotracheal seeding. Evaluation by MRI allows for a comprehensive model with significant potential in the study of lung cancer.