Ex vivo model of non-small cell lung cancer using mouse lung epithelial cells

Taku Sato, Mami Morita, Ryota Tanaka, Yui Inoue, Miyuki Nomura, Yoshimi Sakamoto, Koh Miura, Shigemi Ito, Ikuro Sato, Nobuyuki Tanaka, Jiro Abe, Satomi Takahashi, Masaaki Kawai, Masami Sato, Yoshitaka Hippo, Hiroshi Shima, Yoshinori Okada, Nobuhiro Tanuma

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Lung cancer is the most common cause of cancer mortality, however, efficient methods to culture, expand and transform lung epithelial (LE) cells have not been established. In the present study, an efficient ex vivo method was applied to recapitulate lung carcinogenesis using mouse LE cells. A Matrigel-assisted three-dimensional culture was used to isolate and selectively expand LE cells from mouse lungs. Purified LE cells were passaged and expanded for at least 2 to 3 months while maintaining epidermal growth factor-dependence. LE cells were also easily transformed by genetic manipulations using retroviral vectors. A SV40 large-T antigen, suppressing p53 and pRB, plus an activated oncogene, such as KrasG12V or EGFRex19del, were required to transform LE cells. Transformed cells formed tumors resembling non-small cell lung cancer (NSCLC) in allograft models and exhibited strong oncogene addiction. This experimental system provided a unique model system to study lung tumorigenesis and develop novel therapeutics against NSCLC.

Original languageEnglish
Pages (from-to)6863-6868
Number of pages6
JournalOncology Letters
Volume14
Issue number6
DOIs
Publication statusPublished - 2017 Dec

Keywords

  • EGFR
  • Kras
  • Lung cancer
  • Non-small cell lung cancer
  • Tumorigenesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Sato, T., Morita, M., Tanaka, R., Inoue, Y., Nomura, M., Sakamoto, Y., Miura, K., Ito, S., Sato, I., Tanaka, N., Abe, J., Takahashi, S., Kawai, M., Sato, M., Hippo, Y., Shima, H., Okada, Y., & Tanuma, N. (2017). Ex vivo model of non-small cell lung cancer using mouse lung epithelial cells. Oncology Letters, 14(6), 6863-6868. https://doi.org/10.3892/ol.2017.7098