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Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells

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Abstract

Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30–40% are unable to receive the standard treatment due to invasive diseases. Therefore, novel therapies are required for their treatment. Although patient-derived cell lines are important tools for basic and pre-clinical research, PMP cell lines derived from patients with HGMCP-S have never been reported. Thus, we established a novel PMP cell line NCC-PMP2-C1, using surgically resected tumor tissue from a patient with HGMCP-S. NCC-PMP2-C1 cells were maintained for more than five months and passaged 30 times under culture conditions. NCC-PMP2-C1 cells exhibited multiple deletions and somatic mutations, slow growth, histological features, and dissemination of tumor cells in nude mice. Screening for the anti-proliferative effects of anti-cancer drugs on cells revealed that bortezomib, mubritinib, and romidepsin had a significant response against NCC-PMP2-C1 cells. Thus, the NCC-PMP2-C1 cell line is the first PMP cell line harboring signet ring cells and will be a valuable resource for basic and preclinical studies of HGMCP-S.

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Acknowledgements

We would like to thank Editage (www.editage.jp) for English language editing and constructive comments on the manuscript.

Funding

This research was supported by JSPS KAKENHI (Grant Number 21K08743).

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Authors and Affiliations

  1. Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Rei Noguchi, Yuki Yoshimatsu, Yooksil Sin, Takuya Ono, Ryuto Tsuchiya & Tadashi Kondo

  2. Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan

    Hiroshi Yoshida

  3. Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan

    Tohru Kiyono

  4. NPO to Support Peritoneal Surface Malignancy Treatment, Japanese/Asian School of Peritoneal Surface Oncology, Kyoto, Japan

    Yutaka Yonemura

  5. Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan

    Yutaka Yonemura

  6. Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga, Japan

    Yutaka Yonemura

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  1. Rei Noguchi
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Contributions

Conceptualization, R.N. and T.K.; methodology, R.N., Y.Y., and T.K.; software, R.N.; validation, R.N., Y.S., and Y.Y.; formal analysis, Y.S, R.T., T.O. and H.Y.; investigation, R.N.; resources, T.K. and Y.Y.; data curation, R.N.; writing—original draft preparation, R.N. and T.K.; writing—review and editing, T.K.; visualization, R.N.; supervision, R.N., Y.Y., T.K., and T.K.; project administration, R.N. and T.K.; funding acquisition, R.N. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Tadashi Kondo.

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The use of clinical materials for this study was approved by the ethical committees of the National Cancer Center (2018–371) and Kusatsu General Hospital. Informed consent was obtained from all donors.

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Noguchi, R., Yoshimatsu, Y., Sin, Y. et al. Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells. Human Cell 37, 511–522 (2024). https://doi.org/10.1007/s13577-023-01015-0

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