title: Aberrant expression of mucin core proteins and o-linked glycans associated with progression of pancreatic cancer.
abstract: OBJECTIVE
  Mucin expression is a common feature of most adenocarcinomas and features prominently in current attempts to improve diagnosis and therapy for pancreatic cancer and other adenocarcinomas. We investigated the expression of a number of mucin core proteins and associated O-linked glycans expressed in pancreatic adenocarcinoma-sialyl Tn (STn), Tn, T antigen, sialyl Lewis A (CA19-9), sialyl Lewis C (SLeC), Lewis X (LeX), and sialyl LeX (SLeX)-during the progression of pancreatic cancer from early stages to metastatic disease.
  
  
  METHODS
  Immunohistochemical analyses of mucin and associated glycan expression on primary tumor and liver metastatic tumor samples were conducted with matched sets of tissues from 40 autopsy patients diagnosed with pancreatic adenocarcinoma, 14 surgically resected tissue samples, and 8 normal pancreata.
  
  
  RESULTS
  There were significant changes in mucin expression patterns throughout disease progression. MUC1 and MUC4 were differentially glycosylated as the disease progressed from early pancreatic intraepithelial neoplasias to metastatic disease. De novo expression of several mucins correlated with increased metastasis indicating a potentially more invasive phenotype, and we show the expression of MUC6 in acinar cells undergoing acinar to ductal metaplasia. A "cancer field-effect" that included changes in mucin protein expression and glycosylation in the adjacent normal pancreas was also seen.
  
  
  CONCLUSIONS
  There are significant alterations in mucin expression and posttranslational processing during progression of pancreatic cancer from early lesions to metastasis. The results are presented in the context of how mucins influence the biology of tumor cells and their microenvironment during progression of pancreatic cancer.
authors: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
authors: Neeley
authors: N
authors: Remmers
authors: Judy M
authors: JM
authors: Anderson
authors: Erin M
authors: EM
authors: Linde
authors: Dominick J
authors: DJ
authors: DiMaio
authors: Audrey J
authors: AJ
authors: Lazenby
authors: Hans H
authors: HH
authors: Wandall
authors: Ulla
authors: U
authors: Mandel
authors: Henrik
authors: H
authors: Clausen
authors: Fang
authors: F
authors: Yu
authors: Michael A
authors: MA
authors: Hollingsworth
mesh_terms: D061354:Acinar Cells / Q000378:metabolism / Q000473:pathology; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000957:Antigens, Viral, Tumor / Q000378:metabolism; D001344:Autopsy; D018395:CA-19-9 Antigen; D018450:Disease Progression; D005260:Female; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism; D055264:Mucin-4 / Q000378:metabolism; D055272:Mucin-6 / Q000378:metabolism; D009077:Mucins / Q000096:biosynthesis*; D009844:Oligosaccharides / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011134:Polysaccharides / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis; D000080506:Sialyl Lewis X Antigen
chemical_list: D000957:Antigens, Viral, Tumor; D018395:CA-19-9 Antigen; C060192:MUC1 protein, human; C524658:MUC4 protein, human; C524734:MUC6 protein, human; D018396:Mucin-1; D055264:Mucin-4; D055272:Mucin-6; D009077:Mucins; D009844:Oligosaccharides; D011134:Polysaccharides; D020033:Protein Isoforms; D000080506:Sialyl Lewis X Antigen