Abstract

The MUC4 mucin is a high molecular weight membrane-bound glycoprotein. It is aberrantly expressed in pancreatic tumors and tumor cell lines with no detectable expression in the normal pancreas. A progressive increase of MUC4 expression has also been observed in pancreatic intraepithelial neoplasia, suggesting its association with disease development. Here, we investigated the consequences of silencing MUC4 expression in an aggressive and highly metastatic pancreatic tumor cell line CD18/HPAF that expresses high levels of MUC4. The expression of MUC4 was down-regulated by the stable integration of a plasmid-construct expressing antisense-MUC4 RNA. A decrease in MUC4 expression, confirmed by Western blot and immunofluorescence analyses, resulted in diminished growth and clonogenic ability of antisense-MUC4-transfected (EIAS19) cells compared with parental, empty vector (ZEO) and sense transfected (ES6) control cells. In addition, EIAS19 cells displayed a significant decrease in tumor growth and metastatic properties when transplanted orthotopically into the immunodeficient mice. In vitro biological assays for motility, adhesion, and aggregation demonstrated a 3-fold decrease in motility of EIAS19 cells compared with control cells, whereas these cells adhered more and showed an increase in cellular aggregation. Interestingly, MUC4 down-regulation also correlated with the reduced expression of its putative interacting partner, HER2/neu, in antisense-MUC4-transfected cells. In conclusion, the present work demonstrates, for the first time, a direct association of the MUC4 mucin with the metastatic pancreatic cancer phenotype and provides experimental evidence for a functional role of MUC4 in altered growth and behavioral properties of the tumor cell.

Original languageEnglish (US)
Pages (from-to)622-630
Number of pages9
JournalCancer Research
Volume64
Issue number2
DOIs
StatePublished - Jan 15 2004

Fingerprint

Neoplasm Metastasis
Growth
Neoplasms
Mucins
Tumor Cell Line
Antisense RNA
Membrane Glycoproteins
Pancreatic Neoplasms
Biological Assay
Cell Movement
Fluorescent Antibody Technique
Pancreas
Plasmids
Down-Regulation
Molecular Weight
Western Blotting
Phenotype

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Inhibition of MUC4 Expression Suppresses Pancreatic Tumor Cell Growth and Metastasis. / Singh, Ajay P.; Moniaux, Nicolas; Chauhan, Subhash C.; Meza, Jane L; Batra, Surinder Kumar.

In: Cancer Research, Vol. 64, No. 2, 15.01.2004, p. 622-630.

Research output: Contribution to journalArticle

Singh, Ajay P. ; Moniaux, Nicolas ; Chauhan, Subhash C. ; Meza, Jane L ; Batra, Surinder Kumar. / Inhibition of MUC4 Expression Suppresses Pancreatic Tumor Cell Growth and Metastasis. In: Cancer Research. 2004 ; Vol. 64, No. 2. pp. 622-630.
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abstract = "The MUC4 mucin is a high molecular weight membrane-bound glycoprotein. It is aberrantly expressed in pancreatic tumors and tumor cell lines with no detectable expression in the normal pancreas. A progressive increase of MUC4 expression has also been observed in pancreatic intraepithelial neoplasia, suggesting its association with disease development. Here, we investigated the consequences of silencing MUC4 expression in an aggressive and highly metastatic pancreatic tumor cell line CD18/HPAF that expresses high levels of MUC4. The expression of MUC4 was down-regulated by the stable integration of a plasmid-construct expressing antisense-MUC4 RNA. A decrease in MUC4 expression, confirmed by Western blot and immunofluorescence analyses, resulted in diminished growth and clonogenic ability of antisense-MUC4-transfected (EIAS19) cells compared with parental, empty vector (ZEO) and sense transfected (ES6) control cells. In addition, EIAS19 cells displayed a significant decrease in tumor growth and metastatic properties when transplanted orthotopically into the immunodeficient mice. In vitro biological assays for motility, adhesion, and aggregation demonstrated a 3-fold decrease in motility of EIAS19 cells compared with control cells, whereas these cells adhered more and showed an increase in cellular aggregation. Interestingly, MUC4 down-regulation also correlated with the reduced expression of its putative interacting partner, HER2/neu, in antisense-MUC4-transfected cells. In conclusion, the present work demonstrates, for the first time, a direct association of the MUC4 mucin with the metastatic pancreatic cancer phenotype and provides experimental evidence for a functional role of MUC4 in altered growth and behavioral properties of the tumor cell.",
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