Expression of KL-6/MUC1 in pancreatic cancer tissues and its potential involvement in tumor metastasis.

Aberrant expression of KL-6/MUC1 mucin has been proven to be associated with poorer tumor behavior in many carcinomas. The aim of this study was to evaluate the expression of KL-6/MUC1 in pancreatic cancer tissues and its potential involvement in tumor metastasis. The expression of KL-6/MUC1 in 18 cases of pancreatic ductal carcinoma (PDC), 5 cases of intraductal papillary mucinous tumor (IPMT), and 3 cases of islet cell tumor was detected by immunohistochemical staining. To determine the impact of loss of KL-6/MUC1 expression on pancreatic tumor progression, an siRNA targeting MUC1 was synthesized and transfected into Panc-1 cells and Capan-1 cells to knock down KL-6/MUC1 expression. Down-regulation of KL-6/MUC1 expression was detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. E-cadherin and KL-6 mucin co-expression was detected by immunofluorescence. The expression of E-cadherin and E-cadherin/β-catenin comlex was determined by immunoprecipitation. Cell invasive abilities were detected by invasion assay. Positive KL-6/MUC1 staining was observed in all 18 PDC cases (18/18,100.0%) and 1 metastatic IPMT case (1/5, 20.0%). The results suggested that KL-6/MUC1 overexpression may be associated with more aggressive tumor behavior, although the cases of pancreatic cancer tissues in this study are limited. RT-PCR and western blotting showed that both KL-6/MUC1 mRNA and protein can be effectively silenced. Following KL-6/MUC1 knockdown, E-cadherin expression increased. Also, E-cadherin/β-catenin complex expression increased and the invasive ability of the cells decreased. This study indicated that overexpression of KL-6/MUC1 in pancreatic cancer tissues may be associated with metastasis of pancreatic cancer by regulating E-cadherin and E-cadherin/β-catenin complex expression.

[1]  K. Wilkins,et al.  An update on cancer survival. , 2010, Health reports.

[2]  G. Abou-Alfa,et al.  Pancreatic islet cell carcinoma presenting with concurrent Cushing's and Zollinger-Ellison syndromes: case series and literature review. , 2010, European journal of gastroenterology & hepatology.

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

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

[5]  N. Kokudo,et al.  Effect of benzyl-N-acetyl-α-galactosaminide on KL-6 mucin expression and invasive properties of a human pancreatic carcinoma cell line. , 2008, Drug discoveries & therapeutics.

[6]  大野 哲郎.  Prognostic significance of combined expression of MUC1 and adhesion molecules in advanced gastric cancer , 2007 .

[7]  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.

[8]  Akihito,et al.  Decreased MUC 1 Expression Induces E-Cadherin-mediated Cell Adhesion of Breast Cancer Cell Lines 1 , 2006 .

[9]  M. Makuuchi,et al.  KL-6 mucin expression in carcinoma of the ampulla of Vater: association with cancer progression. , 2005, World journal of gastroenterology.

[10]  A. Hölscher,et al.  MUC1 and Nuclear β-Catenin Are Coexpressed at the Invasion Front of Colorectal Carcinomas and Are Both Correlated with Tumor Prognosis , 2004, Clinical Cancer Research.

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

[12]  M. Hollingsworth,et al.  Nuclear Association of the Cytoplasmic Tail of MUC1 and β-Catenin* , 2003, Journal of Biological Chemistry.

[13]  J. Behrens,et al.  The Wnt signaling pathway and its role in tumor development , 2003, Journal of Cancer Research and Clinical Oncology.

[14]  S. Gendler,et al.  MUC1 alters β-catenin-dependent tumor formation and promotes cellular invasion , 2003, Oncogene.

[15]  A. Sonnenberg,et al.  Episialin ( MUC 1 ) Overexpression Inhibits Integrin-mediated Cell Adhesion to Extracellular Matrix Components , 2002 .

[16]  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.

[17]  L. Yin,et al.  The epidermal growth factor receptor regulates interaction of the human DF3/MUC1 carcinoma antigen with c-Src and beta-catenin. , 2001, The Journal of biological chemistry.

[18]  N. Kohno,et al.  Clinical significance of MUC1 and E-cadherin expression, cellular proliferation, and angiogenesis at the deepest invasive portion of colorectal cancer. , 2000, International journal of oncology.

[19]  D. Kufe,et al.  Interaction of Glycogen Synthase Kinase 3β with the DF3/MUC1 Carcinoma-Associated Antigen and β-Catenin , 1998, Molecular and Cellular Biology.

[20]  N. Kohno,et al.  Decreased MUC1 expression induces E-cadherin-mediated cell adhesion of breast cancer cell lines. , 1998, Cancer research.

[21]  Gerhard Christofori,et al.  A causal role for E-cadherin in the transition from adenoma to carcinoma , 1998, Nature.

[22]  J. Mazeron,et al.  TNM classification of malignant tumours (5 e dition) , 1998 .

[23]  D. Kufe,et al.  Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-associated antigen and beta-catenin. , 1998, Molecular and cellular biology.

[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]  N. Kohno,et al.  Detection of soluble tumor-associated antigens in sera and effusions using novel monoclonal antibodies, KL-3 and KL-6, against lung adenocarcinoma. , 1988, Japanese journal of clinical oncology.

[26]  K. Ohhashi.  Four cases of mucin-producing cancer of the pancreas on specific findings of the papilla of Vater , 1982 .