The aim of this study is to provide a comprehensive characterization of stemness in pancreatic ductal adenocarcinoma (PDAC) cell lines. Seventeen cell lines were evaluated for the expression of cancer stem cell (CSC) markers. The two putative pancreatic CSC phenotypes were expressed heterogeneously ranging from 0 to 99.35% (median 3.46) for ESA(+)CD24(+)CD44(+) and 0 to 1.94% (median 0.13) for CXCR4(+)CD133(+). Cell lines were classified according to ESA(+)CD24(+)CD44(+) expression as: Low-Stemness (LS; <5%, n = 9, median 0.31%); Medium-Stemness (MS; 6-20%, n = 4, median 12.4%); and High-Stemness (HS; >20%, n = 4, median 95.8%) cell lines. Higher degree of stemness was associated with in vivo tumorigenicity but not with in vitro growth kinetics, clonogenicity, and chemo-resistance. A wide characterization (chemokine receptors, factors involved in pancreatic organogenesis, markers of epithelial-mesenchymal transition, and secretome) revealed that the degree of stemness was associated with KRT19 and NKX2.2 mRNA expression, with CD49a and CA19.9/Tie2 protein expression, and with the secretion of VEGF, IL-7, IL-12p70, IL-6, CCL3, IL-10, and CXCL9. The expression of stem cell markers was also evaluated on primary tumor cells from 55 PDAC patients who underwent pancreatectomy with radical intent, revealing that CXCR4(+)/CD133(+) and CD24(+) cells, but not ESA(+)CD24(+)CD44(+), are independent predictors of mortality.

A Comprehensive Characterization of Stemness in Cell Lines and Primary Cells of Pancreatic Ductal Adenocarcinoma

Pasquale, Valentina;Reni, Michele;Piemonti, Lorenzo
Ultimo
2022

Abstract

The aim of this study is to provide a comprehensive characterization of stemness in pancreatic ductal adenocarcinoma (PDAC) cell lines. Seventeen cell lines were evaluated for the expression of cancer stem cell (CSC) markers. The two putative pancreatic CSC phenotypes were expressed heterogeneously ranging from 0 to 99.35% (median 3.46) for ESA(+)CD24(+)CD44(+) and 0 to 1.94% (median 0.13) for CXCR4(+)CD133(+). Cell lines were classified according to ESA(+)CD24(+)CD44(+) expression as: Low-Stemness (LS; <5%, n = 9, median 0.31%); Medium-Stemness (MS; 6-20%, n = 4, median 12.4%); and High-Stemness (HS; >20%, n = 4, median 95.8%) cell lines. Higher degree of stemness was associated with in vivo tumorigenicity but not with in vitro growth kinetics, clonogenicity, and chemo-resistance. A wide characterization (chemokine receptors, factors involved in pancreatic organogenesis, markers of epithelial-mesenchymal transition, and secretome) revealed that the degree of stemness was associated with KRT19 and NKX2.2 mRNA expression, with CD49a and CA19.9/Tie2 protein expression, and with the secretion of VEGF, IL-7, IL-12p70, IL-6, CCL3, IL-10, and CXCL9. The expression of stem cell markers was also evaluated on primary tumor cells from 55 PDAC patients who underwent pancreatectomy with radical intent, revealing that CXCR4(+)/CD133(+) and CD24(+) cells, but not ESA(+)CD24(+)CD44(+), are independent predictors of mortality.
PDAC
pancreatic cancer stem cells
stemness
Biomarkers, Tumor
CD24 Antigen
Cell Line
Cell Line, Tumor
Humans
Hyaluronan Receptors
Integrin alpha1
Interleukin-10
Interleukin-6
Interleukin-7
Neoplastic Stem Cells
RNA, Messenger
Receptors, CXCR4
Vascular Endothelial Growth Factor A
Carcinoma, Pancreatic Ductal
Pancreatic Neoplasms
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/131953
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