Expression of pancreatic digestive enzymes in normal and pathologic epithelial cells of the human gastrointestinal system

Abstract

Pancreatic digestive enzymes have rarely been reported in human nonpancreatic organs. We examined their expression in the epithelial cells of the nonpancreatic gastrointestinal organs, looking for pancreatic alpha-amylase, trypsin, chymotrypsin and pancreatic lipase. Western blotting, enzyme assay and pancreatic alpha-amylase mRNA were also used in selected specimens. In normal tissues, immunoreactivity of one or more of these enzymes was frequently noted in cells of the salivary glands, stomach, duodenum, large pancreatic ducts, extrahepatic bile ducts and gall bladder. The epithelium of the normal oesophagus, small intestine and colon were consistently negative for these enzymes. In pathologic tissues, immunoreactivity for one or more enzymes was present in epithelial cells of pleomorphic adenomas of the salivary glands, oesophageal squamous cell carcinoma, gastric adenoma and adenocarcinoma, pancreatic adenocarcinoma, cholecystitis, adenocarcinoma of the gall bladder and extrahepatic bile duct, and colon adenoma and adenocarcinoma. Western blotting showed a specific band of each enzyme in some specimens of normal stomach. In situ hybridization for pancreatic alpha-amylase mRNA showed specific signals in the normal stomach, but not in the normal colon. Reverse transcriptase polymerase chain reaction analysis for pancreatic alpha-amylase mRNA revealed specific signals in the normal stomach. Enzyme assay revealed that the stomach and gall bladder showed these activities. The data suggest that pancreatic digestive enzymes are produced by several epithelial cell types of the nonpancreatic gastrointestinal organs, that the organs positive for pancreatic enzyme have a common cell lineage, and that neoplasms continue to express or neoexpress these enzymes after neoplastic transformation.

The expression of the carboxyl ester lipase gene in pancreas and pancreatic adenocarcinomas

“…Kim et al (4) reported trypsin activity in 6/29 human ductal adenocarcinomas, yet active pancreatic lipase only in 1/29. Terada et al (8) reported pancreatic lipase in half of their cases but none of the two groups examined CEL expression. In line with our data other investigators (9,10) noted CEL transcription in 6 examined pancreatic tumor cell lines.…”

“…Acinar enzymes are expressed in adenocarcinomas of the pancreas (4,7,8) and pancreatic cell lines (9,10). Therefore, pancreatic adenocarcinoma-specific CEL expression is feasible but has not been verified.…”

“…At present, the cellular origin of ductal carcinoma of the pancreas has not been clearly determined (2,3): despite the similar morphology of ductal adenocarcinomas of the pancreas to ductal structures, an origin from a stem cell (4) or a transdifferentiation process from other cell types (2,5,6) seems possible. Several studies demonstrated an expression of acinar enzymes in adenocarcinomas of the pancreas (4,7,8). Additionally, in the AR42J cell line derived from a rat tumor and in the human carcinoma cell line MIA PaCa-2 the expression of carboxyl ester lipase (CEL) (in the latter an isoform) was demonstrated (9,10).…”

Human trypsinogens in the pancreas and in cancer

“…However, the nucleotide sequence of TAT-2 and pancreatic trypsin-2 is identical (Sorsa et al, 1997). Since then, trypsinogen immunoreactivity or mRNA has been detected in various cancers like stomach, pancreas, ovary, lung, bladder, esophagus, bile duct, and colon cancers, and carcinoma cell lines (Bernard-Perrone et al, 1998, Hirahara et al, 1995, Hotakainen et al, 2006, Koivunen et al, 1991b, Koshikawa et al, 1992, Koshikawa et al, 1994, Miyagi et al, 1995, Miyata et al, 1999, Nyberg et al, 2002, Ohta et al, 1998, Oyama et al, 2000, Paju et al, 2004, Terada et al, 1995, Terada et al, 1997, Yamashita et al, 2003.…”

Immunofluorescence and Electron-Microscopic Observations of Intermediate Cells in the Pancreas of Mice, Rats and Humans

“…Subsequent in vivo and in vitro immunohistochemical and morphological studies have described several types of intermediate cells in normal and pathological human pancreas [Ulich et al, 1982;Ohta et al, 1994;Terada et al, 1997;Aughsteen, 1999], in streptozotocin-diabetic transgenic mouse pancreas [Gu et al, 1997], in streptozotocindiabetic hamster pancreas subjected to in vitro incubation with local pancreatic growth factors [Rosenberg et al, 1996], and in rat and human pancreases subjected either to subtotal surgical pancreatectomy or to partial duct ligation [Rosenberg, 1995;Bertelli and Bendayan, 1997;Szynaka et al, 1997]. These cells have been classified into acinar-ß (acinar cells containing ß-granules), acinar-· (acinar cells containing ·-granules), ß-acinar (ß-cells containing acinar zymogen granules), ·-acinar (·-cells containing acinar zymogen granules), and duct acinar (excretory duct cells containing amylase) cells.…”