Inhibition of KL-6/MUC1 glycosylation limits aggressive progression of pancreatic cancer.

AIM To evaluate the significance of KL-6/MUC1 (a type of MUC1) glycosylation in pancreatic cancer progression. METHODS KL-6/MUC1 expression was detected by immunohistochemistry in 48 patients with pancreatic duct cell carcinoma. The N-/O-glycosylation inhibitors (tunicamycin and benzyl-N-acetyl-α-galactosaminide) were then used to interfere with KL-6/MUC1 glycosylation in two pancreatic carcinoma cell lines, and the effects on KL-6/MUC1 expression, and cell adhesion and invasion were determined. In addition, protein expression of epithelial-mesenchymal transition markers, E-cadherin and vimentin, were evaluated in cells after treatment with glycosylation inhibitors. RESULTS Overexpression of KL-6/MUC1 was found in all pancreatic cancer tissues, but not in the surrounding normal pancreatic tissues. The expression profile of KL-6/MUC1 was significantly decreased after treatment with the inhibitors. The adhesion and invasive ability of cancer cells were significantly decreased after drug treatment, and increased E-cadherin and decreased vimentin expression were found. CONCLUSION KL-6/MUC1 glycosylation is involved in pancreatic cancer metastasis and invasion. Therapeutic strategies which target this may help control the aggressive behavior of pancreatic cancer cells.

[1]  T. Chua,et al.  MUC1 as a Potential Target in Anticancer Therapies , 2015, American journal of clinical oncology.

[2]  N. Smorodinsky,et al.  Cell Surface-Associated Anti-MUC1-Derived Signal Peptide Antibodies: Implications for Cancer Diagnostics and Therapy , 2014, PloS one.

[3]  H. Wandall,et al.  Potential for novel MUC1 glycopeptide-specific antibody in passive cancer immunotherapy , 2013, Immunopharmacology and immunotoxicology.

[4]  S. Yamada,et al.  Epithelial-to-mesenchymal transition predicts prognosis of pancreatic cancer. , 2013, Surgery.

[5]  S. Batra,et al.  Emerging role of mucins in epithelial to mesenchymal transition. , 2013, Current cancer drug targets.

[6]  S. Cascio,et al.  Altered glycosylation of MUC1 influences its association with CIN85: the role of this novel complex in cancer cell invasion and migration , 2013, Oncotarget.

[7]  Judy M. Anderson,et al.  Aberrant Expression of Mucin Core Proteins and O-Linked Glycans Associated with Progression of Pancreatic Cancer , 2013, Clinical Cancer Research.

[8]  J. Schroeder,et al.  MUC1 and metastatic cancer , 2013, Cell adhesion & migration.

[9]  N. Kokudo,et al.  Expression of KL-6/MUC1 in pancreatic cancer tissues and its potential involvement in tumor metastasis. , 2011, Oncology reports.

[10]  S. Gendler,et al.  MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition , 2010, Oncogene.

[11]  Wei Tang,et al.  Clinicopathology of sialomucin: MUC1, particularly KL-6 mucin, in gastrointestinal, hepatic and pancreatic cancers. , 2009, Bioscience trends.

[12]  Y. Sugawara,et al.  Expression of KL-6 mucin, a human MUC1 mucin, in intrahepatic cholangiocarcinoma and its potential involvement in tumor cell adhesion and invasion. , 2009, Life sciences.

[13]  M. Makuuchi,et al.  Elevation of serum KL-6 mucin levels in patients with cholangiocarcinoma. , 2008, Hepato-gastroenterology.

[14]  M. Makuuchi,et al.  Clinical significance of subcellular localization of KL-6 mucin in primary colorectal adenocarcinoma and metastatic tissues. , 2006, World journal of gastroenterology.

[15]  Kai Simons,et al.  Galectin-4 and sulfatides in apical membrane trafficking in enterocyte-like cells , 2005, The Journal of cell biology.

[16]  R. Schmid,et al.  Pancreatic cancer: basic and clinical aspects. , 2005, Gastroenterology.

[17]  S. Uemoto,et al.  Classification of Pancreatic Cancer: Comparison of Japanese and UICC Classifications , 2004, Pancreas.

[18]  Michael A. Hollingsworth,et al.  Mucins in cancer: protection and control of the cell surface , 2004, Nature Reviews Cancer.

[19]  V. Gouyer,et al.  1-Benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside Blocks the Apical Biosynthetic Pathway in Polarized HT-29 Cells* , 2003, Journal of Biological Chemistry.

[20]  S. Crawley,et al.  N-glycosylation is required for the surface localization of MUC17 mucin. , 2003, International journal of oncology.

[21]  J. Sahel,et al.  Intraductal papillary or mucinous tumors (IPMT) of the pancreas: Report of a case series and review of the literature , 2001, American Journal of Gastroenterology.

[22]  M. Hollingsworth,et al.  Enhancement of metastatic properties of pancreatic cancer cells by MUC1 gene encoding an anti‐adhesion molecule , 2000, International journal of cancer.

[23]  N. Kohno.  [Clinical usefulness of KL-6 as a serum marker of idiopathic interstitial pneumonia]. , 1996, Nihon Kyobu Shikkan Gakkai zasshi.

[24]  N. Kohno,et al.  Difference in sero‐diagnostic values among KL‐6‐associated mucins classified as cluster 9 , 1994, International journal of cancer. Supplement = Journal international du cancer. Supplement.

[25]  W. Yoon,et al.  Effect of benzyl-alpha-GalNAc, an inhibitor of mucin glycosylation, on cancer-associated antigens in human colon cancer cells. , 1992, Oncology research.