Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/ -catenin signalling pathway
Objectives Interaction between neoplastic and stromal cells plays an important role in tumour progression. It was recently found that WNT2 was frequently overexpressed in fibroblasts isolated from tumour tissue tumour fibroblasts (TF) compared with fibroblasts from non-tumour tissue normal fibroblas...
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| Veröffentlicht in: | Gut 2011-12, Vol.60 (12), p.1635-1643 |
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| creator | Fu, L. Zhang, C. Zhang, L.-Y. Dong, S.-S. Lu, L.-H. Chen, J. Dai, Y. Li, Y. Kong, K. L. Kwong, D. L. Guan, X.-Y. |
| description | Objectives Interaction between neoplastic and stromal cells plays an important role in tumour progression. It was recently found that WNT2 was frequently overexpressed in fibroblasts isolated from tumour tissue tumour fibroblasts (TF) compared with fibroblasts from non-tumour tissue normal fibroblasts in oesophageal squamous cell carcinoma (OSCC). This study aimed to investigate the effect of TF-secreted Wnt2 in OSCC development via the tumour-stroma interaction. Methods Quantitative PCR, western blotting, immunohistochemistry and immunofluorescence were used to study the expression pattern of Wnt2 and its effect on the Wnt/β-catenin pathway. A Wnt2-secreting system was established in Chinese hamster ovary cells and its conditioned medium was used to study the role of Wnt2 in cell proliferation and invasion. Results Expression of Wnt2 could only be detected in TF but not in OSCC cancer cell lines. In OSCC tissues, Wnt2(+) cells were mainly detected in the boundary between stroma and tumour tissue or scattered within tumour tissue. In this study, Wnt2-positive OSCC was defined when five or more Wnt2(+) cells were observed in 200x microscopy field. Interestingly, Wnt2-positive OSCC (22/51 cases) was significantly associated with lymph node metastases (p=0.001), advanced TNM stage (p=0.001) and disease-specific survival (p |
| doi_str_mv | 10.1136/gut.2011.241638 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1779350907</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4014321751</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1558-3e7b5007765011a90fddd8f4bba44281ea899f84e8cfbc5d98f8a72577cc71703</originalsourceid><addsrcrecordid>eNo1kE1OwzAQhS0EEqWwZmuJdVo7iWN7iSr-pEpsQCwtxxmnqdI42C6od-AQnIWT4aiwGo3mzZv5HkLXlCwoLaplu4-LnFC6yEtaFeIEzWhZiazIhThFM0Iozxgv5Tm6CGFLCBFC0hn6ehtijgMYDxEaXB9w3O_c3mPb1d7VvQ4x4NG7nYsQ_mepbz2E0LkBdwN2ENy40S3oHhs9GPCTjzax-9Bx0jiL4wZwOrX8-c6MjjCktdC1g-77bmjxqOPmUx8u0ZnVfYCrvzpHr_d3L6vHbP388LS6XWeGMpaQgNeMEM4rlni1JLZpGmHLutZlmQsKWkhpRQnC2NqwRgorNM8Z58ZwykkxRzdH3wTyvocQ1TZhpWeCopzLghFJeFItjyrjXQgerBp9t9P-oChRU-QqRa6myNUx8uIXeQd4kg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1779350907</pqid></control><display><type>article</type><title>Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/ -catenin signalling pathway</title><source>BMJ Journals Online Archive</source><source>PubMed Central</source><creator>Fu, L. ; Zhang, C. ; Zhang, L.-Y. ; Dong, S.-S. ; Lu, L.-H. ; Chen, J. ; Dai, Y. ; Li, Y. ; Kong, K. L. ; Kwong, D. L. ; Guan, X.-Y.</creator><creatorcontrib>Fu, L. ; Zhang, C. ; Zhang, L.-Y. ; Dong, S.-S. ; Lu, L.-H. ; Chen, J. ; Dai, Y. ; Li, Y. ; Kong, K. L. ; Kwong, D. L. ; Guan, X.-Y.</creatorcontrib><description>Objectives Interaction between neoplastic and stromal cells plays an important role in tumour progression. It was recently found that WNT2 was frequently overexpressed in fibroblasts isolated from tumour tissue tumour fibroblasts (TF) compared with fibroblasts from non-tumour tissue normal fibroblasts in oesophageal squamous cell carcinoma (OSCC). This study aimed to investigate the effect of TF-secreted Wnt2 in OSCC development via the tumour-stroma interaction. Methods Quantitative PCR, western blotting, immunohistochemistry and immunofluorescence were used to study the expression pattern of Wnt2 and its effect on the Wnt/β-catenin pathway. A Wnt2-secreting system was established in Chinese hamster ovary cells and its conditioned medium was used to study the role of Wnt2 in cell proliferation and invasion. Results Expression of Wnt2 could only be detected in TF but not in OSCC cancer cell lines. In OSCC tissues, Wnt2(+) cells were mainly detected in the boundary between stroma and tumour tissue or scattered within tumour tissue. In this study, Wnt2-positive OSCC was defined when five or more Wnt2(+) cells were observed in 200x microscopy field. Interestingly, Wnt2-positive OSCC (22/51 cases) was significantly associated with lymph node metastases (p=0.001), advanced TNM stage (p=0.001) and disease-specific survival (p<0.0001). Functional study demonstrated that secreted Wnt2 could promote oesophageal cancer cell growth by activating the Wnt/β-catenin signalling pathway and subsequently upregulated cyclin D1 and c-myc expression. Further study found that Wnt2 could enhance cell motility and invasiveness by inducing epithelial-mesenchymal transition. Conclusions TF-secreted Wnt2 acts as a growth and invasion-promoting factor through activating the canonical Wnt/β-catenin signalling pathway in oesophageal cancer cells.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gut.2011.241638</identifier><identifier>CODEN: GUTTAK</identifier><language>eng</language><publisher>London: BMJ Publishing Group LTD</publisher><subject>Cancer ; Cell growth ; Fibroblasts ; Genes ; Kinases ; Metastasis ; Motility ; Mutation ; Proteins</subject><ispartof>Gut, 2011-12, Vol.60 (12), p.1635-1643</ispartof><rights>Copyright: 2011 (c) 2011, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1558-3e7b5007765011a90fddd8f4bba44281ea899f84e8cfbc5d98f8a72577cc71703</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3183,27901,27902</link.rule.ids></links><search><creatorcontrib>Fu, L.</creatorcontrib><creatorcontrib>Zhang, C.</creatorcontrib><creatorcontrib>Zhang, L.-Y.</creatorcontrib><creatorcontrib>Dong, S.-S.</creatorcontrib><creatorcontrib>Lu, L.-H.</creatorcontrib><creatorcontrib>Chen, J.</creatorcontrib><creatorcontrib>Dai, Y.</creatorcontrib><creatorcontrib>Li, Y.</creatorcontrib><creatorcontrib>Kong, K. L.</creatorcontrib><creatorcontrib>Kwong, D. L.</creatorcontrib><creatorcontrib>Guan, X.-Y.</creatorcontrib><title>Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/ -catenin signalling pathway</title><title>Gut</title><description>Objectives Interaction between neoplastic and stromal cells plays an important role in tumour progression. It was recently found that WNT2 was frequently overexpressed in fibroblasts isolated from tumour tissue tumour fibroblasts (TF) compared with fibroblasts from non-tumour tissue normal fibroblasts in oesophageal squamous cell carcinoma (OSCC). This study aimed to investigate the effect of TF-secreted Wnt2 in OSCC development via the tumour-stroma interaction. Methods Quantitative PCR, western blotting, immunohistochemistry and immunofluorescence were used to study the expression pattern of Wnt2 and its effect on the Wnt/β-catenin pathway. A Wnt2-secreting system was established in Chinese hamster ovary cells and its conditioned medium was used to study the role of Wnt2 in cell proliferation and invasion. Results Expression of Wnt2 could only be detected in TF but not in OSCC cancer cell lines. In OSCC tissues, Wnt2(+) cells were mainly detected in the boundary between stroma and tumour tissue or scattered within tumour tissue. In this study, Wnt2-positive OSCC was defined when five or more Wnt2(+) cells were observed in 200x microscopy field. Interestingly, Wnt2-positive OSCC (22/51 cases) was significantly associated with lymph node metastases (p=0.001), advanced TNM stage (p=0.001) and disease-specific survival (p<0.0001). Functional study demonstrated that secreted Wnt2 could promote oesophageal cancer cell growth by activating the Wnt/β-catenin signalling pathway and subsequently upregulated cyclin D1 and c-myc expression. Further study found that Wnt2 could enhance cell motility and invasiveness by inducing epithelial-mesenchymal transition. Conclusions TF-secreted Wnt2 acts as a growth and invasion-promoting factor through activating the canonical Wnt/β-catenin signalling pathway in oesophageal cancer cells.</description><subject>Cancer</subject><subject>Cell growth</subject><subject>Fibroblasts</subject><subject>Genes</subject><subject>Kinases</subject><subject>Metastasis</subject><subject>Motility</subject><subject>Mutation</subject><subject>Proteins</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNo1kE1OwzAQhS0EEqWwZmuJdVo7iWN7iSr-pEpsQCwtxxmnqdI42C6od-AQnIWT4aiwGo3mzZv5HkLXlCwoLaplu4-LnFC6yEtaFeIEzWhZiazIhThFM0Iozxgv5Tm6CGFLCBFC0hn6ehtijgMYDxEaXB9w3O_c3mPb1d7VvQ4x4NG7nYsQ_mepbz2E0LkBdwN2ENy40S3oHhs9GPCTjzax-9Bx0jiL4wZwOrX8-c6MjjCktdC1g-77bmjxqOPmUx8u0ZnVfYCrvzpHr_d3L6vHbP388LS6XWeGMpaQgNeMEM4rlni1JLZpGmHLutZlmQsKWkhpRQnC2NqwRgorNM8Z58ZwykkxRzdH3wTyvocQ1TZhpWeCopzLghFJeFItjyrjXQgerBp9t9P-oChRU-QqRa6myNUx8uIXeQd4kg</recordid><startdate>20111201</startdate><enddate>20111201</enddate><creator>Fu, L.</creator><creator>Zhang, C.</creator><creator>Zhang, L.-Y.</creator><creator>Dong, S.-S.</creator><creator>Lu, L.-H.</creator><creator>Chen, J.</creator><creator>Dai, Y.</creator><creator>Li, Y.</creator><creator>Kong, K. L.</creator><creator>Kwong, D. L.</creator><creator>Guan, X.-Y.</creator><general>BMJ Publishing Group LTD</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope></search><sort><creationdate>20111201</creationdate><title>Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/ -catenin signalling pathway</title><author>Fu, L. ; Zhang, C. ; Zhang, L.-Y. ; Dong, S.-S. ; Lu, L.-H. ; Chen, J. ; Dai, Y. ; Li, Y. ; Kong, K. L. ; Kwong, D. L. ; Guan, X.-Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1558-3e7b5007765011a90fddd8f4bba44281ea899f84e8cfbc5d98f8a72577cc71703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Cancer</topic><topic>Cell growth</topic><topic>Fibroblasts</topic><topic>Genes</topic><topic>Kinases</topic><topic>Metastasis</topic><topic>Motility</topic><topic>Mutation</topic><topic>Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fu, L.</creatorcontrib><creatorcontrib>Zhang, C.</creatorcontrib><creatorcontrib>Zhang, L.-Y.</creatorcontrib><creatorcontrib>Dong, S.-S.</creatorcontrib><creatorcontrib>Lu, L.-H.</creatorcontrib><creatorcontrib>Chen, J.</creatorcontrib><creatorcontrib>Dai, Y.</creatorcontrib><creatorcontrib>Li, Y.</creatorcontrib><creatorcontrib>Kong, K. L.</creatorcontrib><creatorcontrib>Kwong, D. L.</creatorcontrib><creatorcontrib>Guan, X.-Y.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Science Journals</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fu, L.</au><au>Zhang, C.</au><au>Zhang, L.-Y.</au><au>Dong, S.-S.</au><au>Lu, L.-H.</au><au>Chen, J.</au><au>Dai, Y.</au><au>Li, Y.</au><au>Kong, K. L.</au><au>Kwong, D. L.</au><au>Guan, X.-Y.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/ -catenin signalling pathway</atitle><jtitle>Gut</jtitle><date>2011-12-01</date><risdate>2011</risdate><volume>60</volume><issue>12</issue><spage>1635</spage><epage>1643</epage><pages>1635-1643</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><coden>GUTTAK</coden><abstract>Objectives Interaction between neoplastic and stromal cells plays an important role in tumour progression. It was recently found that WNT2 was frequently overexpressed in fibroblasts isolated from tumour tissue tumour fibroblasts (TF) compared with fibroblasts from non-tumour tissue normal fibroblasts in oesophageal squamous cell carcinoma (OSCC). This study aimed to investigate the effect of TF-secreted Wnt2 in OSCC development via the tumour-stroma interaction. Methods Quantitative PCR, western blotting, immunohistochemistry and immunofluorescence were used to study the expression pattern of Wnt2 and its effect on the Wnt/β-catenin pathway. A Wnt2-secreting system was established in Chinese hamster ovary cells and its conditioned medium was used to study the role of Wnt2 in cell proliferation and invasion. Results Expression of Wnt2 could only be detected in TF but not in OSCC cancer cell lines. In OSCC tissues, Wnt2(+) cells were mainly detected in the boundary between stroma and tumour tissue or scattered within tumour tissue. In this study, Wnt2-positive OSCC was defined when five or more Wnt2(+) cells were observed in 200x microscopy field. Interestingly, Wnt2-positive OSCC (22/51 cases) was significantly associated with lymph node metastases (p=0.001), advanced TNM stage (p=0.001) and disease-specific survival (p<0.0001). Functional study demonstrated that secreted Wnt2 could promote oesophageal cancer cell growth by activating the Wnt/β-catenin signalling pathway and subsequently upregulated cyclin D1 and c-myc expression. Further study found that Wnt2 could enhance cell motility and invasiveness by inducing epithelial-mesenchymal transition. Conclusions TF-secreted Wnt2 acts as a growth and invasion-promoting factor through activating the canonical Wnt/β-catenin signalling pathway in oesophageal cancer cells.</abstract><cop>London</cop><pub>BMJ Publishing Group LTD</pub><doi>10.1136/gut.2011.241638</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Cancer Cell growth Fibroblasts Genes Kinases Metastasis Motility Mutation Proteins |
| title | Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/ -catenin signalling pathway |
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