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

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

  • Oncol Lett. 2017 Dec;14(6):6863-6868. doi: 10.3892/ol.2017.7098.
Taku Sato 1 2 3,  Mami Morita 1,  Ryota Tanaka 1 2 3,  Yui Inoue 1,  Miyuki Nomura 1,  Yoshimi Sakamoto 1,  Koh Miura 4,  Shigemi Ito 1,  Ikuro Sato 5,  Nobuyuki Tanaka 6,  Jiro Abe 2,  Satomi Takahashi 2,  Masaaki Kawai 7,  Masami Sato 8,  Yoshitaka Hippo 9,  Hiroshi Shima 1 10,  Yoshinori Okada 3,  Nobuhiro Tanuma 1 10
Affiliations

Affiliations

  • 1 Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Natori, Miyagi 981-1293, Japan.
  • 2 Department of Thoracic Surgery, Miyagi Cancer Center Hospital, Natori, Miyagi 981-1293, Japan.
  • 3 Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
  • 4 Department of Surgery, Miyagi Cancer Center Research Institute, Natori, Miyagi 981-1293, Japan.
  • 5 Tissue Bank, Miyagi Cancer Center Research Institute, Natori, Miyagi 981-1293, Japan.
  • 6 Division of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori, Miyagi 981-1293, Japan.
  • 7 Department of Breast Oncology, Miyagi Cancer Center Research Institute, Natori, Miyagi 981-1293, Japan.
  • 8 Department of General Thoracic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima 890-8544, Japan.
  • 9 Division of Molecular Carcinogenesis, Chiba Cancer Center Research Institute, Chiba, Chiba 260-8717, Japan.
  • 10 Division of Cancer Molecular Biology, Tohoku University Graduate School of Medicine, Natori, Miyagi 981-1293, Japan.
PMID: 29344123 DOI: 10.3892/ol.2017.7098
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.

Keywords

EGFR; Kras; lung cancer; non-small cell lung cancer; tumorigenesis.

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