Please use this identifier to cite or link to this item: https://doi.org/10.1093/carcin/bgp001
DC FieldValue
dc.titleDifferential roles for membrane-bound and soluble syndecan-1 (CD138) in breast cancer progression
dc.contributor.authorNikolova, V.
dc.contributor.authorKoo, C.-Y.
dc.contributor.authorIbrahim, S.A.
dc.contributor.authorWang, Z.
dc.contributor.authorSpillmann, D.
dc.contributor.authorDreier, R.
dc.contributor.authorKelsch, R.
dc.contributor.authorFischgräbe, J.
dc.contributor.authorSmollich, M.
dc.contributor.authorRossi, L.H.
dc.contributor.authorSibrowski, W.
dc.contributor.authorWülfing, P.
dc.contributor.authorKiesel, L.
dc.contributor.authorYip, G.W.
dc.contributor.authorGötte, M.
dc.date.accessioned2015-09-07T09:55:37Z
dc.date.available2015-09-07T09:55:37Z
dc.date.issued2009
dc.identifier.citationNikolova, V., Koo, C.-Y., Ibrahim, S.A., Wang, Z., Spillmann, D., Dreier, R., Kelsch, R., Fischgräbe, J., Smollich, M., Rossi, L.H., Sibrowski, W., Wülfing, P., Kiesel, L., Yip, G.W., Götte, M. (2009). Differential roles for membrane-bound and soluble syndecan-1 (CD138) in breast cancer progression. Carcinogenesis 30 (3) : 397-407. ScholarBank@NUS Repository. https://doi.org/10.1093/carcin/bgp001
dc.identifier.issn01433334
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/120682
dc.description.abstractThe heparan sulfate proteoglycan syndecan-1 (Sdc1) modulates cell proliferation, adhesion, migration and angiogenesis. Proteinase-mediated shedding converts Sdc1 from a membrane-bound coreceptor into a soluble effector capable of binding the same ligands. In breast carcinomas, Sdc1 overexpression correlates with poor prognosis and an aggressive phenotype. To distinguish between the roles of membrane-bound and shed forms of Sdc1 in breast cancer progression, human MCF-7 breast cancer cells were stably transfected with plasmids overexpressing wild-type (WT), constitutively shed and uncleavable forms of Sdc1. Overexpression of WT Sdc1 increased cell proliferation, whereas overexpression of constitutively shed Sdc1 decreased proliferation. Fibroblast growth factor-2-mediated mitogen-activated protein kinase signaling was reduced following small-interfering RNA (siRNA)-mediated knockdown of Sdc1 expression. Constitutively, membrane-bound Sdc1 inhibited invasiveness, whereas soluble Sdc1 promoted invasion of MCF-7 cells into matrigel matrices. The latter effect was reversed by the matrix metalloproteinase inhibitors N isobutyl-N-(4-methoxyphenylsufonyl) glycyl hydroxamic acid and tissue inhibitor of metalloproteinase (TIMP)-1. Affymetrix microarray analysis identified TIMP-1, Furin and urokinase-type plasminogen activator receptor as genes differentially regulated in soluble Sdc1-overexpressing cells. Endogenous TIMP-1 expression was reduced in cells overexpressing soluble Sdc1 and increased in those overexpressing the constitutively membrane-bound Sdc1. Moreover, E-cadherin protein expression was downregulated in cells overexpressing soluble Sdc1. Our results suggest that the soluble and membrane-bound forms of Sdc1 play different roles at different stages of breast cancer progression. Proteolytic conversion of Sdc1 from a membrane-bound into a soluble molecule marks a switch from a proliferative to an invasive phenotype, with implications for breast cancer diagnostics and potential glycosaminoglycan-based therapies. © The Author 2009. Published by Oxford University Press. All rights reserved.
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentANATOMY
dc.description.doi10.1093/carcin/bgp001
dc.description.sourcetitleCarcinogenesis
dc.description.volume30
dc.description.issue3
dc.description.page397-407
dc.description.codenCRNGD
dc.identifier.isiut000263944500003
Appears in Collections:Staff Publications

Show simple item record
Files in This Item:
There are no files associated with this item.

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.