Journal of Cancer Research and Clinical Oncology

, Volume 139, Issue 9, pp 1471–1480 | Cite as

A patient-derived xenograft mouse model generated from primary cultured cells recapitulates patient tumors phenotypically and genetically

  • Hyang Sook Seol
  • Young-Ah Suh
  • Young-joon Ryu
  • Hyun Jung Kim
  • Sung Min Chun
  • Deuk Chae Na
  • Hiroshi Fukamachi
  • Seong-Yun Jeong
  • Eun Kyung Choi
  • Se Jin Jang
Original Paper

Abstract

Background

Preclinical trials of cancer therapeutics require both in vitro and in vivo evaluations. Recently, a patient-derived xenograft model in immunodeficient mice has been reported as a valuable in vivo evaluation system. In our current study, we aimed to establish a more efficient and accurate system for preclinical trials by generating primary cancer cells from patients and performing xenograft transfers of these cells into mice.

Methods

Human lung cancer specimens (n = 4) obtained from chemo-naive patients were cultured in bronchiolar epithelial basal medium supplemented with growth factors, followed by inoculation into non-obese diabetic/severe combined immunodeficient mice. The generated tumors in the mice were validated phenotypically and genetically using the original specimen and primary cancer cells.

Results

Immunohistochemical analysis of marker proteins, including cytokeratin 7, cytokeratin 20, epidermal growth factor receptor, thyroid transcription factor-1, CD56, chromogranin, and synaptophysin, demonstrated that the xenograft tumors were originated from the patient tumors. Moreover, mutation profiling using the OncoMap System, which analyzes mutations at 440 sites in 41 tumor-related genes, showed the same patterns in both the patient and xenograft tumors.

Conclusions

These results indicate that our animal system is suitable for the amplification of patient tumors and will therefore be beneficial for both in vivo and in vitro assessments and preclinical trials of chemotherapeutics. This has the potential to provide a very effective tool for future personalized therapy and for conducting translational lung cancer research.

Keywords

Patient-derived primary cancer cells Xenograft model Lung cancer OncoMap 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Hyang Sook Seol
    • 1
    • 4
  • Young-Ah Suh
    • 1
    • 2
    • 3
  • Young-joon Ryu
    • 4
  • Hyun Jung Kim
    • 1
  • Sung Min Chun
    • 4
  • Deuk Chae Na
    • 1
  • Hiroshi Fukamachi
    • 6
  • Seong-Yun Jeong
    • 1
    • 2
    • 3
  • Eun Kyung Choi
    • 1
    • 2
    • 3
    • 5
  • Se Jin Jang
    • 1
    • 2
    • 3
    • 4
  1. 1.Asan Institute for Life Science, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  2. 2.Institute for Innovative Cancer ResearchAsan Medical CenterSeoulKorea
  3. 3.Center for Development and Commercialization of Anti-Cancer TherapeuticsAsan Medical CenterSeoulKorea
  4. 4.Department of Pathology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  5. 5.Department of Radiation Oncology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  6. 6.Department of Molecular OncologyTokyo Medical and Dental UniversityTokyoJapan

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