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dc.contributor.authorHowlett, M
dc.contributor.authorJudd, LM
dc.contributor.authorJenkins, B
dc.contributor.authorLa Gruta, NL
dc.contributor.authorGrail, D
dc.contributor.authorErnst, M
dc.contributor.authorGiraud, AS
dc.date.available2014-05-21T19:34:17Z
dc.date.available2005-06-09
dc.date.available2005-06-09
dc.date.available2005-06-09
dc.date.available2005-06-09
dc.date.available2005-06-09
dc.date.available2005-06-09
dc.date.available2005-06-09
dc.date.available2005-06-09
dc.date.available2005-06-09
dc.date.available2005-06-09
dc.date.available2005-06-09
dc.date.issued2005-09-01
dc.identifierpii: S0016-5085(05)01356-9
dc.identifier.citationHowlett, M., Judd, L. M., Jenkins, B., La Gruta, N. L., Grail, D., Ernst, M. & Giraud, A. S. (2005). Differential regulation of gastric tumor growth by cytokines that signal exclusively through the coreceptor gp130. GASTROENTEROLOGY, 129 (3), pp.1005-1018. https://doi.org/10.1053/j.gastro.2005.06.068.
dc.identifier.issn0016-5085
dc.identifier.urihttp://hdl.handle.net/11343/26475
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractBACKGROUND & AIMS: We have shown that mice with a mutation in gp130 (gp130(757F/F)), the signal transducing receptor for interleukin (IL)-6 family cytokines, have chronic gastric inflammation and develop distal stomach tumors associated with deregulated phosphorylated STAT3 expression. This model recapitulates many characteristics of intestinal-type gastric cancer in humans. METHODS: To evaluate the role of IL-6 and IL-11 as ligands regulating tumor growth and submucosal invasion, we compared tumor characteristics of gp130(757F/F) mice with gp130(757F/F) mice lacking IL-6 or mature T and B cells. RESULTS: As a result of the gp130(757F/F) mutation, expression of IL-6 and IL-11 was greatly up-regulated concomitant with activation of STAT3 and development of tumors. However, the lack of IL-6 or T and B cells did not impact on tumor growth. While IL-6 did not regulate tumor growth or tumor vascularization, gp130(757F/F)/IL-6(-/-) mice showed approximately 10-20-fold more submucosal tumor invasion, reduced mononuclear inflammatory cell infiltrate, and greater IL-11 and matrix metalloproteinase (MMP)-13 and MMP-9 synthesis than gp130(757F/F) mice. Expression of MMP-13 was largely restricted to tumor-associated stroma, but MMP-9 was also expressed in polymorphonuclear cells and a subset of epithelial cells. In addition, treatment with recombinant IL-11 stimulated expression of MMP-13 and MMP-9 in stomachs of wild-type mice. CONCLUSIONS: Increased submucosal invasion in gp130(757F/F)/IL-6(-/-) mice could not be explained by increased vascularization or reduced immunosurveillance but was most likely facilitated by augmented metalloproteinase activity driven by elevated IL-11 levels.
dc.formatapplication/pdf
dc.languageEnglish
dc.publisherW B SAUNDERS CO-ELSEVIER INC
dc.subjectGastroenterology and Hepatology; Oncology and Carcinogenesis; Cancer and Related Disorders; Digestive System Disorders
dc.titleDifferential regulation of gastric tumor growth by cytokines that signal exclusively through the coreceptor gp130
dc.typeJournal Article
dc.identifier.doi10.1053/j.gastro.2005.06.068
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMedicine - Royal Melbourne And Western Hospitals
melbourne.source.titleGASTROENTEROLOGY
melbourne.source.volume129
melbourne.source.issue3
melbourne.source.pages1005-1018
dc.research.coderfcd321006
dc.research.coderfcd321015
dc.research.codeseo1998730108
dc.research.codeseo1998730113
melbourne.publicationid39804
melbourne.elementsid270105
melbourne.contributor.authorJudd, Louise
melbourne.contributor.authorLa Gruta, Nicole
melbourne.contributor.authorErnst, Matthias
melbourne.contributor.authorGiraud, Andrew
melbourne.contributor.authorJENKINS, BRENDAN
melbourne.contributor.authorHOWLETT, MEEGAN
dc.identifier.eissn1528-0012
pubs.acceptance.date2005-06-09
melbourne.accessrightsThis item is currently not available from this repository


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