title: Development of a human to murine orthotopic xenotransplanted lung cancer model.
abstract: 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.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston 77555-0528, USA. rvertree@utmb.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Vertrees
authors.forename: D J
authors.initials: DJ
authors.lastname: Deyo
authors.forename: M
authors.initials: M
authors.lastname: Quast
authors.forename: K M
authors.initials: KM
authors.lastname: Lightfoot
authors.forename: P J
authors.initials: PJ
authors.lastname: Boor
authors.forename: J B
authors.initials: JB
authors.lastname: Zwischenberger
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology; D015197:Carcinogenicity Tests; D002461:Cell Line, Transformed / Q000637:transplantation; D004195:Disease Models, Animal; D005260:Female; D006470:Hemorrhage / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary / Q000601:surgery*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous / Q000379:methods*