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Article: Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/β-catenin signalling pathway

TitleWnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/β-catenin signalling pathway
Authors
Issue Date2011
PublisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
Citation
Gut, 2011, v. 60 n. 12, p. 1635-1643 How to Cite?
AbstractObjectives: 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 2003X 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.
Persistent Identifierhttp://hdl.handle.net/10722/137266
ISSN
2015 Impact Factor: 14.921
2015 SCImago Journal Rankings: 6.474
ISI Accession Number ID
Funding AgencyGrant Number
National Natural Science Foundation of China30700462
30772475
Major State Basic Research Program of China2006CB910104
University of Hong Kong200907176114
Sun Yat-Sen University85000-3171311
Research Grant CouncilHKU 7656/07M
Funding Information:

This work was supported by grants from the National Natural Science Foundation of China (no 30700462 and no 30772475), grants from the Major State Basic Research Program of China (2006CB910104), the University of Hong Kong Small Project Funding Program (200907176114), Sun Yat-Sen University 'Hundred Talents Program' (85000-3171311) and Research Grant Council grant (HKU 7656/07M).

References

 

DC FieldValueLanguage
dc.contributor.authorFu, Len_HK
dc.contributor.authorZhang, Cen_HK
dc.contributor.authorZhang, LYen_HK
dc.contributor.authorDong, SSen_HK
dc.contributor.authorLu, LHen_HK
dc.contributor.authorChen, Jen_HK
dc.contributor.authorDai, Yen_HK
dc.contributor.authorLi, Yen_HK
dc.contributor.authorKong, KLen_HK
dc.contributor.authorKwong, DLen_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2011-08-26T14:22:04Z-
dc.date.available2011-08-26T14:22:04Z-
dc.date.issued2011en_HK
dc.identifier.citationGut, 2011, v. 60 n. 12, p. 1635-1643en_HK
dc.identifier.issn0017-5749en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137266-
dc.description.abstractObjectives: 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 2003X 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.en_HK
dc.languageengen_US
dc.publisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/en_HK
dc.relation.ispartofGuten_HK
dc.rightsGut. Copyright © BMJ Publishing Group.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshEsophageal Neoplasms - physiopathology - secretion-
dc.subject.meshFibroblasts - physiology - secretion-
dc.subject.meshNeoplasm Invasiveness - physiopathology-
dc.subject.meshWnt Signaling Pathway - physiology-
dc.subject.meshWnt2 Protein - physiology - secretion-
dc.titleWnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/β-catenin signalling pathwayen_HK
dc.typeArticleen_HK
dc.identifier.emailFu, L:gracefu@graduate.hku.hken_HK
dc.identifier.emailKwong, DL:dlwkwong@hku.hken_HK
dc.identifier.emailGuan, XY:xyguan@hkucc.hku.hken_HK
dc.identifier.authorityFu, L=rp01435en_HK
dc.identifier.authorityKwong, DL=rp00414en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1136/gut.2011.241638en_HK
dc.identifier.pmid21672941-
dc.identifier.scopuseid_2-s2.0-80655149144en_HK
dc.identifier.hkuros203473en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80655149144&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume60en_HK
dc.identifier.issue12en_HK
dc.identifier.spage1635en_HK
dc.identifier.epage1643en_HK
dc.identifier.eissn1468-3288-
dc.identifier.isiWOS:000296774500004-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridFu, L=22979236700en_HK
dc.identifier.scopusauthoridZhang, C=54418300600en_HK
dc.identifier.scopusauthoridZhang, LY=35225404400en_HK
dc.identifier.scopusauthoridDong, SS=35788109500en_HK
dc.identifier.scopusauthoridLu, LH=54417625600en_HK
dc.identifier.scopusauthoridChen, J=54416971500en_HK
dc.identifier.scopusauthoridDai, Y=37014328400en_HK
dc.identifier.scopusauthoridLi, Y=36078824800en_HK
dc.identifier.scopusauthoridKong, KL=36106004300en_HK
dc.identifier.scopusauthoridKwong, DL=15744231600en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK

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