Pathobiological implications of MUC16 expression in pancreatic cancer

Dhanya Haridas, Subhankar Chakraborty, Moorthy Palanimuthu Ponnusamy, Imayavaramban Lakshmanan, Satyanarayana Rachagani, Eric Cruz, Sushil Kumar, Srustidhar Das, Subodh M Lele, Judy M. Anderson, Uwe A. Wittel, Michael A Hollingsworth, Surinder Kumar Batra

Research output: Contribution to journalArticle

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Abstract

MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.

Original languageEnglish (US)
Article numbere26839
JournalPloS one
Volume6
Issue number10
DOIs
StatePublished - Nov 4 2011

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pancreatic neoplasms
Pancreatic Neoplasms
Tissue
Tumors
Cells
metastasis
Biomarkers
Mucins
Microarrays
Liver
Ducts
lesions (animal)
Neoplasm Metastasis
Proteins
Molecular weight
pancreatitis
Association reactions
Messenger RNA
Pancreatitis
neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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Pathobiological implications of MUC16 expression in pancreatic cancer. / Haridas, Dhanya; Chakraborty, Subhankar; Palanimuthu Ponnusamy, Moorthy; Lakshmanan, Imayavaramban; Rachagani, Satyanarayana; Cruz, Eric; Kumar, Sushil; Das, Srustidhar; Lele, Subodh M; Anderson, Judy M.; Wittel, Uwe A.; Hollingsworth, Michael A; Batra, Surinder Kumar.

In: PloS one, Vol. 6, No. 10, e26839, 04.11.2011.

Research output: Contribution to journalArticle

Haridas, Dhanya ; Chakraborty, Subhankar ; Palanimuthu Ponnusamy, Moorthy ; Lakshmanan, Imayavaramban ; Rachagani, Satyanarayana ; Cruz, Eric ; Kumar, Sushil ; Das, Srustidhar ; Lele, Subodh M ; Anderson, Judy M. ; Wittel, Uwe A. ; Hollingsworth, Michael A ; Batra, Surinder Kumar. / Pathobiological implications of MUC16 expression in pancreatic cancer. In: PloS one. 2011 ; Vol. 6, No. 10.
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