Dept. of Medicine, Univ. of Oklahoma Health Sciences Center, Oklahoma City, 73104, USA.
Am J Physiol Gastrointest Liver Physiol. 2010 Aug;299(2):G303-10. doi: 10.1152/ajpgi.00146.2010. Epub 2010 Jun 3.
Stem cells are critical in maintaining adult homeostasis and have been proposed to be the origin of many solid tumors, including pancreatic cancer. Here we demonstrate the expression patterns of the putative intestinal stem cell marker DCAMKL-1 in the pancreas of uninjured C57BL/6 mice compared with other pancreatic stem/progenitor cell markers. We then determined the viability of isolated pancreatic stem/progenitor cells in isotransplantation assays following DCAMKL-1 antibody-based cell sorting. Sorted cells were grown in suspension culture and injected into the flanks of athymic nude mice. Here we report that DCAMKL-1 is expressed in the main pancreatic duct epithelia and islets, but not within acinar cells. Coexpression was observed with somatostatin, NGN3, and nestin, but not glucagon or insulin. Isolated DCAMKL-1+ cells formed spheroids in suspension culture and induced nodule formation in isotransplantation assays. Analysis of nodules demonstrated markers of early pancreatic development (PDX-1), glandular epithelium (cytokeratin-14 and Ep-CAM), and isletlike structures (somatostatin and secretin). These data taken together suggest that DCAMKL-1 is a novel putative stem/progenitor marker, can be used to isolate normal pancreatic stem/progenitors, and potentially regenerates pancreatic tissues. This may represent a novel tool for regenerative medicine and a target for anti-stem cell-based therapeutics in pancreatic cancer.
干细胞在维持成人内稳态方面起着至关重要的作用,并且被认为是许多实体肿瘤(包括胰腺癌)的起源。在这里,我们展示了在未受伤的 C57BL/6 小鼠的胰腺中,与其他胰腺干细胞/祖细胞标记物相比,假定的肠干细胞标记物 DCAMKL-1 的表达模式。然后,我们在基于 DCAMKL-1 抗体的细胞分选后的同系移植实验中确定了分离的胰腺干细胞/祖细胞的活力。分选后的细胞在悬浮培养中生长,并注入无胸腺裸鼠的侧腹。在这里,我们报告 DCAMKL-1 在主胰管上皮和胰岛中表达,但不在腺泡细胞中表达。与生长抑素、NGN3 和巢蛋白共表达,但与胰高血糖素或胰岛素不共表达。分离的 DCAMKL-1+细胞在悬浮培养中形成球体,并在同系移植实验中诱导结节形成。对结节的分析显示了早期胰腺发育(PDX-1)、腺上皮(角蛋白-14 和 Ep-CAM)和胰岛样结构(生长抑素和分泌素)的标志物。这些数据表明,DCAMKL-1 是一种新的假定的干细胞/祖细胞标记物,可用于分离正常的胰腺干细胞/祖细胞,并可能再生胰腺组织。这可能代表再生医学的一种新工具,也是胰腺癌基于抗干细胞治疗的一个靶点。