Department of Clinical Physiopathology, University of Turin, and Department of Medical Oncology, Azienda Ospedaliera Universitaria San Giovanni Battista, Turin, Italy.
Oncol Rep. 2012 Jan;27(1):69-76. doi: 10.3892/or.2011.1461. Epub 2011 Sep 14.
Chemoresistance and self-renewal of cancer stem cells (CSC), found in many tumors including pancreatic ductal adenocarcinoma (PDAC), are believed to underlie tumor mass regrowth. The distribution of cells carrying the putative stem-cell markers CD133, Nestin, Notch1-4, Jagged1 and 2, ABCG2 and aldehyde dehydrogenase (ALDH1) was assessed immunohistochemically using PDAC and normal pancreas tissue microarrays. The immunoreactivity was semi-quantitatively graded against the normal pancreas and was correlated with the differentiation grade and disease stage. No statistical significant differences were found between normal pancreas and PDAC in the expression of Nestin, Notch1, 3 and 4, ABCG2 or ALDH1. Notch2 and Jagged1 and 2 expression were increased in PDAC. CD133-positive cells were above-normal in PDAC, but the difference was not statistically significant. Nestin, Notch1-4, Jagged1, ABCG2 and ALDH1 immunostaining scores were not correlated with tumor grade or disease stage. CD133 and Notch2 expression was significantly inversely correlated with tumor grade, but not disease stage. Notch3 immunostaining positively correlated with tumor stage, but not with differentiation grade. Jagged2 protein expression correlated inversely with disease stage, but not with tumor grade. From the clinical standpoint, improved delineation of the tumor CSC signature, putatively responsible for tumor initiation and recurrence after initial response to chemotherapy, may offer novel therapeutic targets for this highly lethal cancer.
肿瘤干细胞（CSC）的化学抗性和自我更新能力，在包括胰腺导管腺癌（PDAC）在内的许多肿瘤中都有发现，被认为是肿瘤团块复发的基础。使用 PDAC 和正常胰腺组织微阵列，通过免疫组织化学评估了携带假定干细胞标记物 CD133、Nestin、Notch1-4、Jagged1 和 2、ABCG2 和醛脱氢酶（ALDH1）的细胞的分布。将免疫反应性与正常胰腺进行半定量评分，并与分化程度和疾病阶段相关联。在 Nestin、Notch1、3 和 4、ABCG2 或 ALDH1 的表达方面，正常胰腺和 PDAC 之间没有统计学上的显著差异。Notch2 和 Jagged1 和 2 的表达在 PDAC 中增加。CD133 阳性细胞在 PDAC 中高于正常水平，但差异无统计学意义。Nestin、Notch1-4、Jagged1、ABCG2 和 ALDH1 免疫染色评分与肿瘤分级或疾病阶段均无相关性。CD133 和 Notch2 的表达与肿瘤分级呈显著负相关，但与疾病阶段无关。Notch3 免疫染色与肿瘤分期呈正相关，但与分化程度无关。Jagged2 蛋白表达与疾病阶段呈负相关，但与肿瘤分级无关。从临床角度来看，对肿瘤 CSC 特征的更好描述，可能为这种高度致命的癌症提供新的治疗靶点，这些特征被认为是肿瘤起始和初始化疗反应后复发的原因。
