Bünger S, Barow M, Thorns C, Freitag-Wolf S, Danner S, Tiede S, Pries R, Görg S, Bruch H-P, Roblick U J, Kruse C, Habermann J K
Laboratory for Surgical Research, Department of Surgery, University of Lübeck, Lübeck, Germany.
Eur Surg Res. 2012;49(2):88-98. doi: 10.1159/000341669. Epub 2012 Aug 30.
Pancreatic cancer is one of the most deadly malignancies with insufficient therapeutic options and poor outcome. Cancer stem cells (CSCs) are thought to be responsible for progression and therapy resistance. We investigated the potential of pancreatic cell lines for CSC research by analyzing to what extent they contain CSC populations and how representative these are compared to clinical tissue.
Six pancreatic cancer cell lines were analyzed by flow cytometry for CD326, CD133, CD44, CD24, CXCR4 and ABCG2. Subsequently, 70 primary pancreatic tissues were evaluated for CD326, CD133 and CD44 by immunohistochemistry.
All the cell lines but one showed a stable expression pattern throughout biological replicates. Marker expression in clinical tissue of CD44 distinguished normal patients from pancreatic carcinoma patients with a sensitivity of 50% at 80% specificity and metastasized from nonmetastasized carcinomas with 69% sensitivity at 100% specificity.
Our results indicate a link between elevated CD44 expression, malignancy and metastasis of pancreatic tissue. Furthermore, individual pancreatic cell lines show a substantial amount of cells with CSC properties which is comparable with interpatient variability detected in primary tissue. These pancreatic cancer cell lines could thus serve for urgently needed pharmacological CSC in vitro research.
胰腺癌是最致命的恶性肿瘤之一,治疗选择有限且预后不佳。癌症干细胞(CSC)被认为与肿瘤进展和治疗耐药性有关。我们通过分析胰腺癌细胞系中CSC群体的含量以及与临床组织相比的代表性,来研究其用于CSC研究的潜力。
采用流式细胞术分析6种胰腺癌细胞系的CD326、CD133、CD44、CD24、CXCR4和ABCG2。随后,通过免疫组织化学评估70例原发性胰腺组织的CD326、CD133和CD44。
除一种细胞系外,所有细胞系在生物学重复实验中均表现出稳定的表达模式。CD44在临床组织中的表达可区分正常患者与胰腺癌患者,在特异性为80%时敏感性为50%,区分转移癌与非转移癌时,在特异性为100%时敏感性为69%。
我们的结果表明CD44表达升高与胰腺组织的恶性程度和转移之间存在联系。此外,个别胰腺癌细胞系显示出大量具有CSC特性的细胞,这与在原发性组织中检测到的患者间变异性相当。因此,这些胰腺癌细胞系可用于急需的CSC体外药理学研究。