Pathobiological implications of MUC16 expression in pancreatic cancer
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. T...
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| Veröffentlicht in: | PloS one 2011-10, Vol.6 (10), p.e26839 |
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| creator | Haridas, Dhanya Chakraborty, Subhankar Ponnusamy, Moorthy P Lakshmanan, Imayavaramban Rachagani, Satyanarayana Cruz, Eric Kumar, Sushil Das, Srustidhar Lele, Subodh M Anderson, Judy M Wittel, Uwe A Hollingsworth, Michael A Batra, Surinder K |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0026839 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0026839</identifier><identifier>PMID: 22066010</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; Analysis ; Biochemistry ; Biology ; Biomarkers ; Biotechnology ; Blotting, Western ; CA-125 Antigen - genetics ; CA-125 Antigen - metabolism ; Cancer ; Cancer metastasis ; Cancer research ; Cancer therapies ; Cell growth ; Cell Line, Tumor ; Deoxyribonucleic acid ; Development and progression ; DNA ; DNA methylation ; Extracellular matrix ; Gene expression ; Gene Expression Regulation, Neoplastic ; Health aspects ; Humans ; Immunohistochemistry ; Invasiveness ; Lesions ; Liver ; Lungs ; Lymph nodes ; Medical imaging ; Medical prognosis ; Medicine ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Metastases ; Metastasis ; Microscopy, Confocal ; Molecular biology ; Molecular weight ; mRNA ; Mucin ; Mucins ; Neoplasm Metastasis ; Omentum ; Ovarian cancer ; Ovarian carcinoma ; Pancreatic cancer ; Pancreatic Ducts - metabolism ; Pancreatic Ducts - pathology ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Pancreatitis ; Pathology ; Patients ; Polymerase chain reaction ; Prognosis ; Proteins ; Quality ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; Tissues ; Tomography</subject><ispartof>PloS one, 2011-10, Vol.6 (10), p.e26839</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Haridas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Haridas et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-de9eddf4df149560d820b9de8f91cf5fe73258a331dbb3ee22e91ece8b1d2d323</citedby><cites>FETCH-LOGICAL-c757t-de9eddf4df149560d820b9de8f91cf5fe73258a331dbb3ee22e91ece8b1d2d323</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204976/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3204976/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22066010$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Srivastava, Rakesh K.</contributor><creatorcontrib>Haridas, Dhanya</creatorcontrib><creatorcontrib>Chakraborty, Subhankar</creatorcontrib><creatorcontrib>Ponnusamy, Moorthy P</creatorcontrib><creatorcontrib>Lakshmanan, Imayavaramban</creatorcontrib><creatorcontrib>Rachagani, Satyanarayana</creatorcontrib><creatorcontrib>Cruz, Eric</creatorcontrib><creatorcontrib>Kumar, Sushil</creatorcontrib><creatorcontrib>Das, Srustidhar</creatorcontrib><creatorcontrib>Lele, Subodh M</creatorcontrib><creatorcontrib>Anderson, Judy M</creatorcontrib><creatorcontrib>Wittel, Uwe A</creatorcontrib><creatorcontrib>Hollingsworth, Michael A</creatorcontrib><creatorcontrib>Batra, Surinder K</creatorcontrib><title>Pathobiological implications of MUC16 expression in pancreatic cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - pathology</subject><subject>Analysis</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Biotechnology</subject><subject>Blotting, Western</subject><subject>CA-125 Antigen - genetics</subject><subject>CA-125 Antigen - metabolism</subject><subject>Cancer</subject><subject>Cancer metastasis</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Extracellular matrix</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Invasiveness</subject><subject>Lesions</subject><subject>Liver</subject><subject>Lungs</subject><subject>Lymph nodes</subject><subject>Medical imaging</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Microscopy, Confocal</subject><subject>Molecular biology</subject><subject>Molecular weight</subject><subject>mRNA</subject><subject>Mucin</subject><subject>Mucins</subject><subject>Neoplasm Metastasis</subject><subject>Omentum</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Ducts - metabolism</subject><subject>Pancreatic Ducts - pathology</subject><subject>Pancreatic Neoplasms - 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implications of MUC16 expression in pancreatic cancer</title><author>Haridas, Dhanya ; Chakraborty, Subhankar ; Ponnusamy, Moorthy P ; Lakshmanan, Imayavaramban ; Rachagani, Satyanarayana ; Cruz, Eric ; Kumar, Sushil ; Das, Srustidhar ; Lele, Subodh M ; Anderson, Judy M ; Wittel, Uwe A ; Hollingsworth, Michael A ; Batra, Surinder K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-de9eddf4df149560d820b9de8f91cf5fe73258a331dbb3ee22e91ece8b1d2d323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - pathology</topic><topic>Analysis</topic><topic>Biochemistry</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Biotechnology</topic><topic>Blotting, Western</topic><topic>CA-125 Antigen - genetics</topic><topic>CA-125 Antigen - metabolism</topic><topic>Cancer</topic><topic>Cancer 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one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haridas, Dhanya</au><au>Chakraborty, Subhankar</au><au>Ponnusamy, Moorthy P</au><au>Lakshmanan, Imayavaramban</au><au>Rachagani, Satyanarayana</au><au>Cruz, Eric</au><au>Kumar, Sushil</au><au>Das, Srustidhar</au><au>Lele, Subodh M</au><au>Anderson, Judy M</au><au>Wittel, Uwe A</au><au>Hollingsworth, Michael A</au><au>Batra, Surinder K</au><au>Srivastava, Rakesh K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pathobiological implications of MUC16 expression in pancreatic cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-10-31</date><risdate>2011</risdate><volume>6</volume><issue>10</issue><spage>e26839</spage><pages>e26839-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22066010</pmid><doi>10.1371/journal.pone.0026839</doi><tpages>e26839</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-10, Vol.6 (10), p.e26839 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1309828128 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenocarcinoma Adenocarcinoma - genetics Adenocarcinoma - pathology Analysis Biochemistry Biology Biomarkers Biotechnology Blotting, Western CA-125 Antigen - genetics CA-125 Antigen - metabolism Cancer Cancer metastasis Cancer research Cancer therapies Cell growth Cell Line, Tumor Deoxyribonucleic acid Development and progression DNA DNA methylation Extracellular matrix Gene expression Gene Expression Regulation, Neoplastic Health aspects Humans Immunohistochemistry Invasiveness Lesions Liver Lungs Lymph nodes Medical imaging Medical prognosis Medicine Membrane Proteins - genetics Membrane Proteins - metabolism Metastases Metastasis Microscopy, Confocal Molecular biology Molecular weight mRNA Mucin Mucins Neoplasm Metastasis Omentum Ovarian cancer Ovarian carcinoma Pancreatic cancer Pancreatic Ducts - metabolism Pancreatic Ducts - pathology Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Pancreatitis Pathology Patients Polymerase chain reaction Prognosis Proteins Quality Reverse Transcriptase Polymerase Chain Reaction RNA Tissues Tomography |
| title | Pathobiological implications of MUC16 expression in pancreatic cancer |
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