Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Sci Rep. 2019 Feb 27;9(1):2876. doi: 10.1038/s41598-019-38988-8.
The Sialyl Lewis A antigen, or CA 19-9, is the prototype serum biomarker for adenocarcinoma of the pancreas. Despite extensive clinical study of CA 19-9 in gastrointestinal malignancies, surprisingly little is known concerning the specific cell types that express this marker during development, tissue regeneration and neoplasia. SOX9 is a transcription factor that plays a key role in these processes in foregut tissues. We report the biochemistry and tissue expression of the GCTM-5 antigen, a pancreatic cancer marker related to, but distinct from, CA19-9. This antigen, defined by two monoclonal antibodies recognising separate epitopes on a large glycoconjugate protein complex, is co-expressed with SOX9 by foregut ductal progenitors in the developing human liver and pancreas, and in pancreatic adenocarcinoma. These progenitors are distinct from cell populations identified by DCLK1, LGR5, or canonical markers of liver and pancreatic progenitor cells. Co-expression of this antigen complex and SOX9 also characterises the ductal metaplasia of submucosal glands that occurs during the development of Barrett's oesophagus. The GCTM-5 antigen complex can be detected in the sera of patients with pancreatic adenocarcinoma. The GCTM-5 epitope shows a much more restricted pattern of expression in the normal adult pancreas relative to CA19-9. Our findings will aid in the identification, characterisation, and monitoring of ductal progenitor cells during development and progression of pancreatic adenocarcinoma in man.
唾液酸化路易斯 A 抗原（Sialyl Lewis A antigen），又称 CA19-9，是胰腺腺癌的典型血清生物标志物。尽管对胃肠道恶性肿瘤中 CA19-9 进行了广泛的临床研究，但人们对该标志物在发育、组织再生和肿瘤形成过程中表达的特定细胞类型却知之甚少。SOX9 是一种转录因子，在前肠组织的这些过程中发挥着关键作用。我们报告了 GCTM-5 抗原的生物化学和组织表达，这是一种与 CA19-9 相关但又不同的胰腺癌标志物。该抗原由两个单克隆抗体识别一种大糖缀合蛋白复合物上的两个不同表位而定义，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达，在前肠导管祖细胞中与 SOX9 共同表达。这些祖细胞与由 DCLK1、LGR5 或肝和胰腺祖细胞的经典标志物识别的细胞群不同。该抗原复合物和 SOX9 的共表达也表征了发生在 Barrett 食管发育过程中的黏膜下腺的导管化生。该 GCTM-5 抗原复合物可在胰腺腺癌患者的血清中检测到。与 CA19-9 相比，GCTM-5 表位在正常成人胰腺中的表达模式要受限得多。我们的发现将有助于在人类胰腺腺癌的发育和进展过程中识别、表征和监测导管祖细胞。
