Aberrant expression of mucin core proteins and O-linked glycans associated with progression of pancreatic cancer

Neeley Remmers, Judy M. Anderson, Erin M. Linde, Dominick J DiMaio, Audrey J Lazenby, Hans H. Wandall, Ulla Mandel, Henrik Clausen, Fang Yu, Michael A Hollingsworth

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Abstract

Purpose: 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. Experimental Design: 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.

Original languageEnglish (US)
Pages (from-to)1981-1993
Number of pages13
JournalClinical Cancer Research
Volume19
Issue number8
DOIs
StatePublished - Apr 15 2013

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Mucins
Pancreatic Neoplasms
Polysaccharides
Proteins
Adenocarcinoma
Neoplasms
Pancreas
Neoplasm Metastasis
Cellular Microenvironment
Acinar Cells
Viral Tumor Antigens
Metaplasia
Glycosylation
Disease Progression
Autopsy
Research Design
Phenotype
Liver

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Aberrant expression of mucin core proteins and O-linked glycans associated with progression of pancreatic cancer. / Remmers, Neeley; Anderson, Judy M.; Linde, Erin M.; DiMaio, Dominick J; Lazenby, Audrey J; Wandall, Hans H.; Mandel, Ulla; Clausen, Henrik; Yu, Fang; Hollingsworth, Michael A.

In: Clinical Cancer Research, Vol. 19, No. 8, 15.04.2013, p. 1981-1993.

Research output: Contribution to journalArticle

Remmers, Neeley ; Anderson, Judy M. ; Linde, Erin M. ; DiMaio, Dominick J ; Lazenby, Audrey J ; Wandall, Hans H. ; Mandel, Ulla ; Clausen, Henrik ; Yu, Fang ; Hollingsworth, Michael A. / Aberrant expression of mucin core proteins and O-linked glycans associated with progression of pancreatic cancer. In: Clinical Cancer Research. 2013 ; Vol. 19, No. 8. pp. 1981-1993.
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AU - Anderson, Judy M.

AU - Linde, Erin M.

AU - DiMaio, Dominick J

AU - Lazenby, Audrey J

AU - Wandall, Hans H.

AU - Mandel, Ulla

AU - Clausen, Henrik

AU - Yu, Fang

AU - Hollingsworth, Michael A

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N2 - Purpose: 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. Experimental Design: 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.

AB - Purpose: 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. Experimental Design: 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.

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