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TADG-12 作为胰腺导管腺癌 (PDAC) 发展的早期标志物:含胰岛素细胞的参与。

TADG-12 as an early marker in the development of pancreatic ductal adenocarcinoma (PDAC): involvement of insulin containing cells.

机构信息

Department of Molecular Cell Biology, The Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel.

Department of Biological Services, The Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel.

出版信息

Acta Histochem. 2014 Jun;116(5):781-7. doi: 10.1016/j.acthis.2014.01.007. Epub 2014 Feb 21.

DOI:10.1016/j.acthis.2014.01.007
PMID:24560937
Abstract

TADG-12 is a serine protease that was characterized as expressed in ovarian and gastric carcinomas. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and its late detection results in poor prognosis. Therefore, we decided to examine whether TADG-12 appears early in PDAC development. In normal pancreas, pale to moderate immunostaining is present in islets of Langerhans, while exocrine tissue and ducts are free from labeling. In contrast, in cancer patients, who still preserve the integrity of the exocrine and the endocrine tissues, a pronounced immunolabelling of TADG-12 was evident mainly located in the insulin containing β cells. In a more progressive stage of the disease TADG-12 was also evident in the deteriorated exocrine tissue. TADG-12 was also heavily labeled in islets of Langerhans, which were embedded in the stroma of the residual pancreatic tissue. Again, there was a considerable overlap between the labeling of insulin and TADG-12 in these islets. Close correlation between insulin and TADG-12 was also evident in islets of Langerhans surrounded by adipose cells. The TADG-12 labeled was confined to the cytoplasm and the membrane of the cells. In the progressive stage of PDAC, the cancerous ducts were clearly labeled with TADG-12 with no labeling of insulin. At high magnification the TADG-12 clearly labeled the cytoplasm and the cell wall membrane of duct cells, while the nuclei remained unstained upon incubation with antibodies to TADG-12. The present findings may assist in early detection of PDAC as well as targeting of TADG-12 in order to attenuate the rapid progression of the disease.

摘要

TADG-12 是一种丝氨酸蛋白酶,其特征在于在卵巢癌和胃癌中表达。胰腺导管腺癌(PDAC)是最致命的癌症之一,其晚期检测导致预后不良。因此,我们决定检查 TADG-12 是否在 PDAC 发展早期出现。在正常胰腺中,胰岛呈淡至中度免疫染色,而外分泌组织和导管无标记。相比之下,在癌症患者中,尽管保留了外分泌和内分泌组织的完整性,但 TADG-12 的明显免疫标记主要位于含有胰岛素的β细胞中。在疾病的更进展阶段,TADG-12 在外分泌组织恶化时也很明显。TADG-12 在胰岛中也被强烈标记,这些胰岛嵌入残余胰腺组织的基质中。同样,这些胰岛中胰岛素和 TADG-12 的标记有相当大的重叠。在被脂肪细胞包围的胰岛中,胰岛素和 TADG-12 之间也存在密切相关性。在 PDAC 的进展阶段,癌细胞导管明显标记有 TADG-12,而无胰岛素标记。在高倍放大下,TADG-12 清楚地标记了导管细胞的细胞质和细胞膜,而用 TADG-12 抗体孵育时细胞核保持未染色。这些发现可能有助于早期检测 PDAC 以及靶向 TADG-12 以减轻疾病的快速进展。

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