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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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Cites
Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery
Datta, S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., & Greenberg, M. E. (1997) · Cell · doi:10.1016/s0092-8674(00)80405-5 · Cited by 5,689
Functions of Cell Surface Heparan Sulfate Proteoglycans
Bernfield, M. R., Götte, M., Park, P. W., Reizes, O., Fitzgerald, M. L., Lincecum, J. M., & Zako, M. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.729 · Cited by 2,722
Yayon, A., Klagsbrun, M., Esko, J. D., Leder, P., & Ornitz, D. M. (1991) · Cell · doi:10.1016/0092-8674(91)90512-w · Cited by 2,440
Interleukin-3-Induced Phosphorylation of BAD Through the Protein Kinase Akt
Peso, L. D., González-Garcı́a, M., Page, C., Herrera, R., & Nuñez, G. (1997) · Science · doi:10.1126/science.278.5338.687 · Cited by 1,797
Schmidt, L. S., Duh, F.-M. C., Chen, F., Kishida, T., Glenn, G. M., Choyke, P. L., Scherer, S. W., Zhuang, Z., Lubensky, I. A., Dean, M. C., et al. (1997) · Nature Genetics · doi:10.1038/ng0597-68 · Cited by 1,517
Requirement of Heparan Sulfate for bFGF-Mediated Fibroblast Growth and Myoblast Differentiation
Rapraeger, A. C., Krufka, A., & Olwin, B. B. (1991) · Science · doi:10.1126/science.1646484 · Cited by 1,508
Ponzetto, C., Bardelli, A., Zhen, Z., Maina, F., Zonca, P. D., Giordano, S., Graziani, A., Panayotou, G., & Comoglio, P. M. (1994) · Cell · doi:10.1016/0092-8674(94)90318-2 · Cited by 994
Multiple Myeloma: Increasing Evidence for a Multistep Transformation Process
Hallek, M. J., Bergsagel, P. L., & Anderson, K. C. (1998) · Blood · doi:10.1182/blood.v91.1.3 · Cited by 750
Regulated Diversity of Heparan Sulfate*
Lindahl, U., Kusche-Gullberg, M., & Kjellén, L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.39.24979 · Cited by 688
Ets transcription factors: nuclear effectors of the Ras–MAP-kinase signaling pathway
Wasylyk, B., Hagman, J. R., & Gutierrez‐Hartmann, A. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01211-0 · Cited by 506
Activating mutations for the Met tyrosine kinase receptor in human cancer
Jeffers, M., Schmidt, L. S., Nakaigawa, N., Webb, C. P., Weirich, G., Kishida, T., Zbar, B., & Woude, G. F. V. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.21.11445 · Cited by 443
Hsueh, Y.-P., Wang, T.-F., Yang, F.-C., & Sheng, M. (2000) · Nature · doi:10.1038/35005118 · Cited by 355
A plasmocyte selective monoclonal antibody (B‐B4) recognizes syndecan‐1
Wijdenes, J., Vooijs, W. C., Clément, C., Post, J., Morard, F., Vita, N., Laurent, P., Sun, R.-X., Klein, B., & Dore, J. (1996) · British Journal of Haematology · doi:10.1046/j.1365-2141.1996.d01-1811.x · Cited by 340
HGF receptor associates with the anti‐apoptotic protein BAG‐1 and prevents cell death.
Bardelli, A., Longati, P., Albero, D., Goruppi, S., Schneider, C., Ponzetto, C., & Comoglio, P. M. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01009.x · Cited by 312
Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice
Alexander, C. M., Reichsman, F., Hinkes, M. T., Lincecum, J., Becker, K. A., Cumberledge, S., & Bernfield, M. (2000) · Nature Genetics · doi:10.1038/77108 · Cited by 305
Zhang, X., Gaillard, J., Robillard, N., Lu, Z., Gu, Z., Jourdan, M., Boiron, J.-M., Bataille, R., & Klein, B. (1994) · Blood · doi:10.1182/blood.v83.12.3654.3654 · Cited by 277
van der Voort, R., Taher, T. E. I., Wielenga, V. T., Spaargaren, M., Prevo, R., Smit, L., David, G., Hartmann, G., Gherardi, E., & Pals, S. T. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6499 · Cited by 232
Self-citationProteoglycans and pattern formation: sugar biochemistry meets developmental genetics
Selleck, S. B. (2000) · Trends in Genetics · doi:10.1016/s0168-9525(00)01997-1 · Cited by 217
Elevated Serum Concentrations of Hepatocyte Growth Factor in Patients With Multiple Myeloma
Seidel, C., Børset, M., Turesson, I., Abildgaard, N., Sundan, A., & Anders Waage for th e Nordic Myeloma Study Group (1998) · Blood · doi:10.1182/blood.v91.3.806 · Cited by 214
Hepatocyte growth factor and its receptor c-met in multiple myeloma
Børset, M., Hjorth‐Hansen, H., Seidel, C., Sundan, A., & Waage, A. (1996) · Blood · doi:10.1182/blood.v88.10.3998.bloodjournal88103998 · Cited by 211
Syndecan-Regulated Receptor Signaling
Rapraeger, A. C. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.149.5.995 · Cited by 197
Dhodapkar, M. V., Abe, E., Theus, A. M., Lacy, M., Langford, J. K., Barlogie, B., & Sanderson, R. D. (1998) · Blood · doi:10.1182/blood.v91.8.2679.2679_2679_2688 · Cited by 196
Takai, K., Hara, J., Matsumoto, K., Hosoi, G., Osugi, Y., Tawa, A., Okada, S., & Nakamura, T. (1997) · Blood · doi:10.1182/blood.v89.5.1560 · Cited by 156
Carbone, A., Gaïdano, G., Gloghini, A., Larocca, L. M., Capello, D., Canzonieri, V., Antinori, A., Tirelli, U., Falini, B., & Dalla‐Favera, R. (1998) · PubMed · doi:10.1182/blood.v91.3.747 · Cited by 133
Børset, M., Lien, E., Espevik, T., Helseth, E., Waage, A., & Sundan, A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.40.24655 · Cited by 131
Lyon, M., & Gallagher, J. T. (1998) · Matrix Biology · doi:10.1016/s0945-053x(98)90096-8 · Cited by 127
Heparin Binding and Oligomerization of Hepatocyte Growth Factor/Scatter Factor Isoforms
Sakata, H., Stahl, S. J., Taylor, W. G., Rosenberg, J. M., Sakaguchi, K., Wingfield, P. T., & Rubin, J. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.14.9457 · Cited by 125
Børset, M., Hjertner, Ø., Yaccoby, S., Epstein, J., & Sanderson, R. D. (2000) · Blood · doi:10.1182/blood.v96.7.2528 · Cited by 121
van der Voort, R., Taher, T. E. I., Keehnen, R. M. J., Smit, L., Groenink, M., & Pals, S. T. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.12.2121 · Cited by 116
Self-citationThe hepatocyte growth factor/ met pathway in development, tumorigenesis, and B-cell differentiation
van der Voort, R., Taher, T. E. I., Derksen, P. W. B., Spaargaren, M., van der Neut, R., & Pals, S. T. (2000) · Advances in cancer research · doi:10.1016/s0065-230x(00)79002-6 · Cited by 112
Self-citationHeparan Sulfate-mediated Cell Aggregation
Stanley, M. J., Liebersbach, B. F., Liu, W., Anhalt, D. J., & Sanderson, R. D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.10.5077 · Cited by 112
Seidel, C., Børset, M., Hjertner, Ø., Cao, D., Abildgaard, N., Hjorth‐Hansen, H., Sanderson, R. D., Waage, A., & Sundan, A. (2000) · Blood · doi:10.1182/blood.v96.9.3139 · Cited by 106
Hartmann, G. R., Prospero, T. D., Brinkmann, V., Ozcelik, Ö., Winter, G. P., Hepple, J., Batley, S., Bladt, F., Sachs, M., Birchmeier, C., et al. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70059-4 · Cited by 96
Weimar, I. S., de Jong, D., Muller, E. J., Nakamura, T., van Gorp, J. M. H. H., GAST, G. C. D., & Gerritsen, W. R. (1997) · Blood · doi:10.1182/blood.v89.3.990 · Cited by 96
Syndecan-1 mediates cell spreading in transfected human lymphoblastoid (Raji) cells.
Lebakken, C. S., & Rapraeger, A. C. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.132.6.1209 · Cited by 84
van der Voort, R., Keehnen, R. M. J., Beuling, E. A., Spaargaren, M., & Pals, S. T. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.8.1115 · Cited by 50
Self-citationCapello, D., Gaïdano, G., Gallicchio, M., Gloghini, A., Médico, E., Vivenza, D., Buonaiuto, D., Fassone, L., Avanzi, G. C., Saglio, G. N., et al. (2000) · Leukemia · doi:10.1038/sj.leu.2401666 · Cited by 40
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Fuster, M. M., & Esko, J. D. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1649 · Cited by 1,389
Roles of heparan-sulphate glycosaminoglycans in cancer
Sasisekharan, R., Shriver, Z. H., Venkataraman, G., & Narayanasami, U. (2002) · Nature reviews. Cancer · doi:10.1038/nrc842 · Cited by 621
Proteoglycans in cancer biology, tumour microenvironment and angiogenesis
Iozzo, R. V., & Sanderson, R. D. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01236.x · Cited by 579
Moreaux, J., Legouffe, E., Jourdan, E., Quittet, P., Rème, T., Lugagne, C., Moine, P., Rossi, J.-F., Klein, B., & Tarte, K. (2004) · Blood · doi:10.1182/blood-2003-06-1984 · Cited by 558
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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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