Expression of cancer stem cell markers in pancreatic intraepithelial neoplasias and pancreatic ductal adenocarcinomas

Kure,Shoko; Matsuda,Yoko; Hagio,Masahito; Ueda,Junji; Naito,Zenya; Ishiwata,Toshiyuki

doi:10.3892/ijo.2012.1565

Expression of cancer stem cell markers in pancreatic intraepithelial neoplasias and pancreatic ductal adenocarcinomas

Authors:
- Shoko Kure
- Yoko Matsuda
- Masahito Hagio
- Junji Ueda
- Zenya Naito
- Toshiyuki Ishiwata
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Affiliations: Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School, Tokyo 113-8602, Japan, Surgery for Organ and Biological Regulation, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8602, Japan
Published online on: July 23, 2012 https://doi.org/10.3892/ijo.2012.1565
Pages: 1314-1324

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Abstract

Cancer stem cells (CSCs) play pivotal roles in cancer growth, invasion, metastasis and recurrence. Several proteins have been reported as CSC markers for pancreatic ductal adenocarcinoma (PDAC). In the present study, we examined the correlation between pancreatic intraepithelial neoplasias (PanINs) and CSC markers including CD24, CD44, CD133, CXCR4, ESA and nestin using immunohistochemical analysis. Furthermore, we examined the roles and clinical significance of these CSC markers in PDAC. CD24-, CD44-, CXCR4-, ESA- and nestin-positive cells were detected in the following tissues, listed in order of increasing percentage: normal ducts < low-grade PanINs < high-grade PanINs < PDACs. CD133 did not increase according to the malignancy grade. In PDAC, cells positive for each of the following CSC markers were detected, listed according to increasing percentage: nestin < CD133 < CD44 < CD24 < CXCR4 < ESA. CXCR4 and ESA expression correlated with well-differentiated PDAC. Venous invasion was positively associated with CD133 and inversely associated with ESA. CSC marker expression levels detected in PDAC cell lines using flow cytometry showed lowest expression of CD133 and highest of CD44, differing from the results obtained using immunohistochemistry. In two PDAC subtypes, adenosquamous carcinoma and anaplastic carcinoma, ESA was expressed more abundantly in adenocarcinoma components, whereas CD44 and nestin showed high expression in anaplastic components. Together, these results suggest that most CSC markers correlate with pancreatic carcinogenesis through the PanIN-to-PDAC sequence. Each CSC marker was related in a different manner with proliferation, differentiation, invasiveness or tissue type of PDAC.

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