Development of a human to murine orthotopic xenotransplanted lung cancer model

R. A.V.P. Ccp, D. J. Deyo, M. Quast, K. M. Lightfoot, P. J. Boor, J. B. Zwischenberger

Research output: Contribution to journalArticle

17 Scopus citations

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 106 cells from either cell line. BEAS2-B cells were nontumorigenic, whereas mice with BZR-T33 cells had tumors (9510 ± 4307 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 106 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 (1120 ± 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 106 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.

Original languageEnglish (US)
Pages (from-to)349-358
Number of pages10
JournalJournal of Investigative Surgery
Volume13
Issue number6
StatePublished - Dec 1 2000

Keywords

  • Lung cancer
  • Metastatic disease
  • Xenotransplantation

ASJC Scopus subject areas

  • Surgery

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  • Cite this

    Ccp, R. A. V. P., Deyo, D. J., Quast, M., Lightfoot, K. M., Boor, P. J., & Zwischenberger, J. B. (2000). Development of a human to murine orthotopic xenotransplanted lung cancer model. Journal of Investigative Surgery, 13(6), 349-358.