Cathepsin&nbsp;B is highly expressed in pancreatic cancer stem‑like cells and is associated with patients' surgical outcomes

Fujimoto,Takuya; Tsunedomi,Ryouichi; Matsukuma,Satoshi; Yoshimura,Kiyoshi; Oga,Atsunori; Fujiwara,Nobuyuki; Fujiwara,Yasuhiro; Matsui,Hiroto; Shindo,Yoshitaro; Tokumitsu,Yukio; Suzuki,Nobuaki; Kobayashi,Shogo; Hazama,Shoichi; Eguchi,Hidetoshi; Nagano,Hiroaki

doi:10.3892/ol.2020.12291

Cathepsin B is highly expressed in pancreatic cancer stem‑like cells and is associated with patients' surgical outcomes

Authors:
- Takuya Fujimoto
- Ryouichi Tsunedomi
- Satoshi Matsukuma
- Kiyoshi Yoshimura
- Atsunori Oga
- Nobuyuki Fujiwara
- Yasuhiro Fujiwara
- Hiroto Matsui
- Yoshitaro Shindo
- Yukio Tokumitsu
- Nobuaki Suzuki
- Shogo Kobayashi
- Shoichi Hazama
- Hidetoshi Eguchi
- Hiroaki Nagano
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Affiliations: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan, Department of Clinical Research in Tumor Immunology, Showa University Clinical Research Institute for Clinical Pharmacology and Therapeutics, Setagaya, Tokyo 157‑8577, Japan, Department of Molecular Pathology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565‑0871, Japan, Department of Translational Research and Developmental Therapeutics Against Cancer, Yamaguchi University School of Medicine, Ube, Yamaguchi 755‑8505, Japan
Published online on: November 11, 2020 https://doi.org/10.3892/ol.2020.12291
Article Number: 30
Copyright: © Fujimoto et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

Cancer stem‑like cells (CSLCs) in solid tumors are resistant to conventional chemotherapy and molecularly targeted therapy, which is thought to contribute to cancer recurrence and metastasis. The present study aimed to identify biomarkers for pancreatic CSLCs (P‑CSLCs). Using our previously reported methods, P‑CSLC‑enriched populations were generated from pancreatic cancer cell lines. The protein expression profiles of these populations were compared with those of parental cells using two‑dimensional electrophoresis, tandem mass spectrometry, flow cytometry and immunohistochemistry. Protein expression in surgical specimens was also evaluated for relationships with clinical outcomes. A lysosomal cysteine protease, cathepsin B (CTSB), was significantly upregulated in P‑CSLCs compared with that in the parental cells, as shown using western blotting. Flow cytometry analysis also confirmed that CTSB was more highly expressed on the surface of P‑CSLCs compared with that on parental cells. Moreover, PCLCs had elevated cellular secretions of CTSB compared with the parental cells. Finally, CTSB expression was evaluated in 69 resected tumor specimens, and high expression was associated with the patients' clinicopathological features and surgical outcomes. The present results suggested that CTSB is a biomarker for poor survival in patients with pancreatic cancer, which is possibly associated with P‑CSLCs. This novel biomarker may also have potential as a therapeutic target.

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