title: TADG-12 as an early marker in the development of pancreatic ductal adenocarcinoma (PDAC): involvement of insulin containing cells.
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.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel. Electronic address: abraham.amsterdam@weizmann.ac.il.
authors.forename: Abraham
authors.initials: A
authors.lastname: Amsterdam
authors.affiliation: Department of Biological Services, The Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel.
authors.forename: Calanit
authors.initials: C
authors.lastname: Raanan
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, 234 Herzl Street, Rehovot 76100, Israel.
authors.forename: Lotem
authors.initials: L
authors.lastname: Shpigner
authors.affiliation: Department of Gastroenterology, Kaplan Medical Center, Rehovot 76100, Israel.
authors.forename: Arafat
authors.initials: A
authors.lastname: Shwiqi
authors.affiliation: Department of Gastroenterology, Kaplan Medical Center, Rehovot 76100, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Melzer
authors.affiliation: Wolfson Hospital, Holon 58100, Israel.
authors.forename: Letizia
authors.initials: L
authors.lastname: Schreiber
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology; D014408:Biomarkers, Tumor; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000201:enzymology / Q000503:physiopathology; D002462:Cell Membrane / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D006801:Humans; D007515:Islets of Langerhans / Q000201:enzymology; D010179:Pancreas / Q000201:enzymology; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000503:physiopathology; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D012697:Serine Endopeptidases; C417724:TADG-12 serine protease
keywords: Invasion of cancer cells; Pancreatic ductal adenocarcinoma; Serine protease; β endocrine cells