Calreticulin is highly expressed in pancreatic cancer stem-like cells

Satoshi Matsukuma, Kiyoshi Yoshimura, Tomio Ueno, Atsunori Oga, Moeko Inoue, Yusaku Watanabe, Atsuo Kuramasu, Masanori Fuse, Ryouichi Tsunedomi, Satoshi Nagaoka, Hidetoshi Eguchi, Hiroto Matsui, Yoshitaro Shindo, Noriko Maeda, Yoshihiro Tokuhisa, Reo Kawano, Tomoko Furuya-Kondo, Hiroshi Itoh, Shigefumi Yoshino, Shoichi HazamaMasaaki Oka, Hiroaki Nagano

研究成果: Contribution to journalArticle査読

14 被引用数 (Scopus)

抄録

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/CD44v9low population was much higher than that in the CRTlow/CD44v9high population. 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.

本文言語英語
ページ(範囲)1599-1609
ページ数11
ジャーナルCancer Science
107
11
DOI
出版ステータス出版済み - 11 1 2016

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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