Derivation of pancreatic acinar cell carcinoma cell line <scp>HS</scp>‐1 as a patient‐derived tumor organoid
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- Daisuke Hoshi
- Department of Molecular Carcinogenesis Chiba Cancer Center Research Institute Chiba Japan
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- Emiri Kita
- Department of Molecular Carcinogenesis Chiba Cancer Center Research Institute Chiba Japan
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- Yoshiaki Maru
- Department of Molecular Carcinogenesis Chiba Cancer Center Research Institute Chiba Japan
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- Hiroyuki Kogashi
- Department of Molecular Carcinogenesis Chiba Cancer Center Research Institute Chiba Japan
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- Yuki Nakamura
- Division of Oncogenomics Chiba Cancer Center Research Institute Chiba Japan
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- Yasutoshi Tatsumi
- Division of Oncogenomics Chiba Cancer Center Research Institute Chiba Japan
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- Osamu Shimozato
- Division of Oncogenomics Chiba Cancer Center Research Institute Chiba Japan
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- Kazuyoshi Nakamura
- Department of Gastroenterology Chiba Cancer Center Chiba Japan
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- Kentaro Sudo
- Department of Gastroenterology Chiba Cancer Center Chiba Japan
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- Akiko Tsujimoto
- Department of Gastroenterology Chiba Cancer Center Chiba Japan
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- Ryo Yokoyama
- Division of Pathological Diagnosis Matsudo City General Hospital Chiba Japan
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- Atsushi Kato
- Department of Hepatobiliary‐Pancreatic Surgery Chiba Cancer Center Chiba Japan
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- Tetsuo Ushiku
- Department of Pathology, Graduate School of Medicine The University of Tokyo Tokyo Japan
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- Masashi Fukayama
- Department of Pathology, Graduate School of Medicine The University of Tokyo Tokyo Japan
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- Makiko Itami
- Division of Surgical Pathology Chiba Cancer Center Chiba Japan
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- Taketo Yamaguchi
- Department of Gastroenterology Chiba Cancer Center Chiba Japan
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- Yoshitaka Hippo
- Department of Molecular Carcinogenesis Chiba Cancer Center Research Institute Chiba Japan
抄録
<jats:title>Abstract</jats:title><jats:p>Acinar cell carcinoma (ACC) of the pancreas is a malignant tumor of the exocrine cell lineage with a poor prognosis. Due to its rare incidence and technical difficulties, few authentic human cell lines are currently available, hampering detailed investigations of ACC. Therefore, we applied the organoid culture technique to various types of specimens, such as bile, biopsy, and resected tumor, obtained from a single ACC patient. Despite the initial propagation, none of these organoids achieved long‐term proliferation or tolerated cryopreservation, confirming the challenging nature of establishing ACC cell lines. Nevertheless, the biopsy‐derived early passage organoid developed subcutaneous tumors in immunodeficient mice. The xenograft tumor histologically resembled the original tumor and gave rise to infinitely propagating organoids with solid features and high levels of trypsin secretion. Moreover, the organoid stained positive for carboxylic ester hydrolase, a specific ACC marker, but negative for the duct cell marker CD133 and the endocrine lineage marker synaptophysin. Hence, we concluded the derivation of a novel ACC cell line of the pure exocrine lineage, designated HS‐1. Genomic analysis revealed extensive copy number alterations and mutations in <jats:italic>EP400</jats:italic> in the original tumor, which were enriched in primary organoids. HS‐1 displayed homozygous deletion of <jats:italic>CDKN2A</jats:italic>, which might underlie xenograft formation from organoids. Although resistant to standard cytotoxic agents, the cell line was highly sensitive to the proteasome inhibitor bortezomib, as revealed by an in vitro drug screen and in vivo validation. In summary, we document a novel ACC cell line, which could be useful for ACC studies in the future.</jats:p>
収録刊行物
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- Cancer Science
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Cancer Science 114 (3), 1165-1179, 2022-11-27
Wiley
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詳細情報 詳細情報について
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- CRID
- 1360861707376882560
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- ISSN
- 13497006
- 13479032
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- データソース種別
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- Crossref
- KAKEN