Development of a human to murine orthotopic xenotransplanted lung cancer model

The goal was to develop a clinically relevant animal model that could be us ed to assess the efficacy of therapeutic interventions in lung cancer. Two cell lines, noncancerous control (BEAS2-B, immortalized human bronchial-epi thelial cell line) and cancerous (BZR-T33, H-ras transformed BEAS2-B) were implanted into nude (athymic) mice. Two groups (n = 10 each) received dorso scapular 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 +/- 4307 mm(3)) confirmed by histology, and a significantly smaller bod y 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) receive d 106 cells from either cell line injected into tail veins. Animals receivi ng BZR-T33 cells had a smaller body weight, palpable lung masses (67%), obv ious tail masses (44%), and average tumor burden (1120 +/- 115 mm(3)), and histology revealed invasion of lung tissue and interstitial hemorrhage. In development of the orthotopic xenotransplanted model, mice (2 groups, n = 1 0 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 t he presence of masses in intubated live mice, later confirmed by histology. In summary, the H-ras transfected cell line developed lung masses followin g tail-vein injection and endotracheal seeding. Evaluation by MRI allows fo r a comprehensive model with significant potential in the study of lung can cer.