Please use this identifier to cite or link to this item:
|Title:||Differential roles for membrane-bound and soluble syndecan-1 (CD138) in breast cancer progression||Authors:||Nikolova, V.
|Issue Date:||2009||Citation:||Nikolova, 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||Abstract:||The 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.||Source Title:||Carcinogenesis||URI:||http://scholarbank.nus.edu.sg/handle/10635/120682||ISSN:||01433334||DOI:||10.1093/carcin/bgp001|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Nov 13, 2019
WEB OF SCIENCETM
checked on Nov 13, 2019
checked on Nov 8, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.