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Ex vivo culture of head and neck cancer explants in cell sheet for testing chemotherapeutic sensitivity

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Tumor explant culture systems can mimic the in vivo tumor microenvironment, proposing as a substitute for preclinical studies for prediction of individual treatment response. Therefore, our study evaluated the potential usefulness of ex vivo tumor explants culture assembled into the cell sheets by anticancer drug screening in patients with head and neck squamous cell carcinoma (HNSCC).

Methods

Our model included tumor explants incorporated into cell sheet composing of epithelium and subepithelial stroma using tumor and mucosal samples obtained from the HNSCC patients who underwent surgery. Cell growth, viability, and hypoxia were measured by cell counting kit-8, live/dead assay, propidium iodide, and LOX-1 staining, and were compared among the different treatment groups with vehicle, cisplatin or docetaxel.

Results

Tumor explants stably survived in the cell sheet over 10 days after explantation, whereas most of the explants in non-matrix culture became nonviable within 5–8 days with the significant daily decrease of viability. The live tissue areas of tumor explants in the cell sheet maintained over 30 days without significant changes although hypoxic cell areas gradually increased up to 5 days. Tissue viability and live cancer tissue areas significantly decreased after the treatment of cisplatin or docetaxel in the dose and time-dependent manners.

Conclusion

Our cell sheet-based tumor explants model might be applied to the reliable ex vivo screening for anticancer chemotherapeutics for HNSCC.

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Funding

This study was supported by the National Research Foundation of Korea (NRF) grant, funded by the Ministry of Science and ICT (MSIT), the Government of Korea (No. 2019R1A2C2002259).

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Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Gyeonggi-do, 13496, Republic of Korea

    Jaewang Lee, Ji Hyeon You & Jong-Lyel Roh

  2. Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea

    Daiha Shin

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  1. Jaewang Lee
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  2. Ji Hyeon You
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  3. Daiha Shin
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  4. Jong-Lyel Roh
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Correspondence to Jong-Lyel Roh.

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The authors have no conflict of interest to disclose.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent from all individual participants was obtained.

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Lee, J., You, J.H., Shin, D. et al. Ex vivo culture of head and neck cancer explants in cell sheet for testing chemotherapeutic sensitivity. J Cancer Res Clin Oncol 146, 2497–2507 (2020). https://doi.org/10.1007/s00432-020-03306-7

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  • DOI: https://doi.org/10.1007/s00432-020-03306-7

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