title: Calreticulin is highly expressed in pancreatic cancer stem-like cells.
abstract: Cancer stem-like cells (CSLCs) in solid tumors are thought to be resistant to conventional chemotherapy or molecular targeting therapy and to contribute to cancer recurrence and metastasis. In this study, we aimed to identify a biomarker of pancreatic CSLCs (P-CSLCs). A P-CSLC-enriched population was generated from pancreatic cancer cell lines using our previously reported method and its protein expression profile was compared with that of parental cells by 2-D electrophoresis and tandem mass spectrometry. The results indicated that a chaperone protein calreticulin (CRT) was significantly upregulated in P-CSLCs compared to parental cells. Flow cytometry analysis indicated that CRT was mostly localized to the surface of P-CSLCs and did not correlate with the levels of CD44v9, another P-CSLC biomarker. Furthermore, the side population in the CRThigh/CD44v9lowpopulation was much higher than that in the CRTlow/CD44v9highpopulation. Calreticulin expression was also assessed by immunohistochemistry in pancreatic cancer tissues (n = 80) obtained after radical resection and was found to be associated with patients' clinicopathological features and disease outcomes in the Cox proportional hazard regression model. Multivariate analysis identified CRT as an independent prognostic factor for pancreatic cancer patients, along with age and postoperative therapy. Our results suggest that CRT can serve as a biomarker of P-CSLCs and a prognostic factor associated with poorer survival of pancreatic cancer patients. This novel biomarker can be considered as a therapeutic target for cancer immunotherapy.
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Satoshi
authors: S
authors: Matsukuma
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Exploratory Oncology Research and Clinical Trial Center, National Cancer Center of Japan, Tokyo, Japan.
authors: Kiyoshi
authors: K
authors: Yoshimura
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Tomio
authors: T
authors: Ueno
authors: Department of Molecular Pathology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Atsunori
authors: A
authors: Oga
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Exploratory Oncology Research and Clinical Trial Center, National Cancer Center of Japan, Tokyo, Japan.
authors: Moeko
authors: M
authors: Inoue
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Yusaku
authors: Y
authors: Watanabe
authors: Department of Molecular Pharmacology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Atsuo
authors: A
authors: Kuramasu
authors: Exploratory Oncology Research and Clinical Trial Center, National Cancer Center of Japan, Tokyo, Japan.
authors: Masanori
authors: M
authors: Fuse
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Ryouichi
authors: R
authors: Tsunedomi
authors: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
authors: Satoshi
authors: S
authors: Nagaoka
authors: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
authors: Hidetoshi
authors: H
authors: Eguchi
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Hiroto
authors: H
authors: Matsui
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Yoshitaro
authors: Y
authors: Shindo
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Noriko
authors: N
authors: Maeda
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Yoshihiro
authors: Y
authors: Tokuhisa
authors: Center for Clinical Research, Yamaguchi University Hospital, Ube, Japan.
authors: Reo
authors: R
authors: Kawano
authors: Department of Molecular Pathology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Tomoko
authors: T
authors: Furuya-Kondo
authors: Department of Molecular Pathology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Hiroshi
authors: H
authors: Itoh
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Oncology Center, Yamaguchi University Hospital, Ube, Japan.
authors: Shigefumi
authors: S
authors: Yoshino
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Shoichi
authors: S
authors: Hazama
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Masaaki
authors: M
authors: Oka
authors: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Hiroaki
authors: H
authors: Nagano
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D051928:CD47 Antigen / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D040901:Proteomics
chemical_list: D018528:ATP-Binding Cassette Transporters; C576483:CALR protein, human; C448906:CD44v9 antigen; D051928:CD47 Antigen; C497894:CD47 protein, human; D037282:Calreticulin; D018960:Hyaluronan Receptors
keywords: Biomarkers; calreticulin; cancer stem cells; pancreatic cancer; proteomics