The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.
Cell surface proteoglycan syndecan-1 mediates hepatocyte growth factor binding and promotes Met signaling in multiple myeloma
Open accessAbstract
Heparan sulfate proteoglycans (HSPGs) play a crucial role in growth regulation by assembling signaling complexes and presenting growth factors to their cognate receptors. Within the immune system, expression of the HSPG syndecan-1 (CD138) is characteristic of terminally differentiated B cells, ie, plasma cells, and their malignant counterpart, multiple myeloma (MM). This study explored the hypothesis that syndecan-1 might promote growth factor signaling and tumor growth in MM. For this purpose, the interaction was studied between syndecan-1 and hepatocyte growth factor (HGF), a putative paracrine and autocrine regulator of MM growth. The study demonstrates that syndecan-1 is capable of binding HGF and that this growth factor is indeed a potent stimulator of MM survival and proliferation. Importantly, the interaction of HGF with heparan sulfate moieties on syndecan-1 strongly promotes HGF-mediated signaling, resulting in enhanced activation of Met, the receptor tyrosine kinase for HGF. Moreover, HGF binding to syndecan-1 promotes activation of the phosphatidylinositol 3-kinase/protein kinase B and RAS/mitogen-activated protein kinase pathways, signaling routes that have been implicated in the regulation of cell survival and proliferation, respectively. These results identify syndecan-1 as a functional coreceptor for HGF that promotes HGF/Met signaling in MM cells, thus suggesting a novel function for syndecan-1 in MM tumorigenesis.
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“The HS chain of SDC1 has been shown to act as a co-receptor for growth factors, promoting the activation of several RTKs, such as EGFR, c-MET, FGFR, and IGF1R.29,30,31,32”
From Therapeutic targeting of syndecan-1 axis overcomes acquired resistance to KRAS-targeted therapy in gastrointestinal cancers (2025) · cites this paper as [30]
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The Glycome of Normal and Malignant Plasma Cells
Moehler, T. M., Seckinger, A., Hose, D., Andrulis, M., Moreaux, J., Hielscher, T., Willhauck-Fleckenstein, M., Merling, A., Bertsch, U., Jauch, A., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083719 · Cited by 17
Theardy, M. S., Takeda, M., Sorokin, A., Chen, S., Yang, Z., Wang, X., Kanikarla, P., Coker, O., Nguyen, P., Wei, Y., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102253 · Cited by 6
Metadata
- Authors
- Derksen, P. W. B., Keehnen, R. M. J., Evers, L. M., van Oers, M. H. J., Spaargaren, M., & Pals, S. T.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2002-02-15
- Volume
- 99
- Issue
- 4
- Pages
- 1405-1410
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2009169267
- Cited by
- 274
- References
- 38
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 7 · 2023: 12 · 2022: 7 · 2021: 10 · 2020: 15 · 2019: 9 · 2018: 10 · 2017: 7 · 2016: 9 · 2015: 10 · 2014: 12 · 2013: 14 · 2012: 14
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- KWF Kankerbestrijding
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- syndecan-1, hepatocyte growth factor, MET receptor tyrosine kinase, multiple myeloma, heparan sulfate proteoglycans, co-receptors, PI3K/Akt signaling, Ras/MEK/ERK signaling, cell proliferation and survival, tumor growth
- MeSH terms
- Cell Division, Enzyme Activation, Humans, Membrane Glycoproteins, Multiple Myeloma, Protein Binding, Proteoglycans, Proto-Oncogene Proteins, Transfection, Tumor Cells, Cultured, Signal Transduction, Hepatocyte Growth Factor, Protein Serine-Threonine Kinases, ras Proteins, Proto-Oncogene Proteins c-met, Phosphatidylinositol 3-Kinases, MAP Kinase Signaling System, Proto-Oncogene Proteins c-akt, Syndecans, Syndecan-1
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