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dc.contributor.authorHaupt, Larisa
dc.contributor.authorW. Thompson, Erik
dc.contributor.authorTrezise, Ann
dc.contributor.authorE. Irving, Rachel
dc.contributor.authorG. Irving, Michael
dc.contributor.authorGriffiths, Lyn
dc.date.accessioned2017-08-11T01:06:27Z
dc.date.available2017-08-11T01:06:27Z
dc.date.issued2006
dc.date.modified2007-08-07T04:40:11Z
dc.identifier.issn1471-2407
dc.identifier.doi10.1186/1471-2407-6-18
dc.identifier.urihttp://hdl.handle.net/10072/12345
dc.description.abstractBackground: Members of the matrix metalloproteinase (MMP) family of proteases are required for the degradation of the basement membrane and extracellular matrix in both normal and pathological conditions. In vitro, MT1-MMP (MMP-14, membrane type-1-MMP) expression is higher in more invasive human breast cancer (HBC) cell lines, whilst in vivo its expression has been associated with the stroma surrounding breast tumours. MMP-1 (interstitial collagenase) has been associated with MDA-MB-231 invasion in vitro, while MMP-3 (stromelysin-1) has been localised around invasive cells of breast tumours in vivo. As MMPs are not stored intracellularly, the ability to localise their expression to their cells of origin is difficult. Methods: We utilised the unique in situ-reverse transcription-polymerase chain reaction (IS-RT-PCR) methodology to localise the in vitro and in vivo gene expression of MT1-MMP, MMP-1 and MMP-3 in human breast cancer. In vitro, MMP induction was examined in the MDA-MB-231 and MCF-7 HBC cell lines following exposure to Concanavalin A (Con A). In vivo, we examined their expression in archival paraffin embedded xenografts derived from a range of HBC cell lines of varied invasive and metastatic potential. Mouse xenografts are heterogenous, containing neoplastic human parenchyma with mouse stroma and vasculature and provide a reproducible in vivo model system correlated to the human disease state. Results: In vitro, exposure to Con A increased MT1-MMP gene expression in MDA-MB-231 cells and decreased MT1-MMP gene expression in MCF-7 cells. MMP-1 and MMP-3 gene expression remained unchanged in both cell lines. In vivo, stromal cells recruited into each xenograft demonstrated differences in localised levels of MMP gene expression. Specifically, MDA-MB-231, MDA-MB-435 and Hs578T HBC cell lines are able to influence MMP gene expression in the surrounding stroma. Conclusion: We have demonstrated the applicability and sensitivity of IS-RT-PCR for the examination of MMP gene expression both in vitro and in vivo. Induction of MMP gene expression in both the epithelial tumour cells and surrounding stromal cells is associated with increased metastatic potential. Our data demonstrate the contribution of the stroma to epithelial MMP gene expression, and highlight the complexity of the role of MMPs in the stromal-epithelial interactions within breast carcinoma.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent53872 bytes
dc.format.extent1772802 bytes
dc.format.mimetypetext/plain
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherBioMed Central
dc.publisher.placeUnited Kingdom
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto10
dc.relation.ispartofjournalBMC Cancer
dc.relation.ispartofvolume6
dc.rights.retentionY
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchcode3211
dc.titleIn vitro and in vivo MMP gene expression localisation by In Situ-RT-PCR in cell culture and paraffin embedded human breast cancer cell line xenografts.
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/2.0
dc.description.versionVersion of Record (VoR)
gro.description.notepublicPage numbers are not for citation purposes. Instead, this article has the unique article number of 18.
gro.rights.copyright© 2006 Haupt et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.date.issued2006
gro.hasfulltextFull Text
gro.griffith.authorHaupt, Larisa
gro.griffith.authorGriffiths, Lyn


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