Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-11

AUTHORS

K Mahtouk, F W Cremer, T Rème, M Jourdan, M Baudard, J Moreaux, G Requirand, G Fiol, J De Vos, M Moos, P Quittet, H Goldschmidt, J-F Rossi, D Hose, B Klein

ABSTRACT

The epidermal growth factor (EGF)/EGF-receptor (ErbB1-4) family is involved in the biology of multiple myeloma (MM). In particular, ErbB-specific inhibitors induce strong apoptosis of myeloma cells (MMC) in vitro. To delineate the contribution of the 10 EGF-family ligands to the pathogenesis of MM, we have assessed their expression and biological activity. Comparing Affymetrix DNA-microarray-expression-profiles of CD138-purified plasma-cells from 65 MM-patients and 7 normal individuals to those of plasmablasts and B-cells, we found 5/10 EGF-family genes to be expressed in MMC. Neuregulin-2 and neuregulin-3 were expressed by MMC only, while neuregulin-1, amphiregulin and transforming growth factor-alpha were expressed by both MMC and normal plasma-cells. Using real-time polymerase chain reaction, we found HB-EGF, amphiregulin, neuregulin-1 and epiregulin to be expressed by cells from the bone marrow-environment. Only the EGF-members able to bind heparan-sulphate proteoglycans (HSPGs) - neuregulin-1, amphiregulin, HB-EGF - promote the growth of MMC. Those ligands strongly bind MMC through HSPGs. The binding and the MMC growth activity was abrogated by heparitinase, heparin or deletion of the HS-binding domain. The number of HS-binding EGF ligand molecules bound to MMC was higher than 10(5) molecules/cell and paralleled that of syndecan-1. Syndecan-1, the main HSPG present on MM cells, likely concentrates high levels of HS-binding-EGF-ligands at the cell membrane and facilitates ErbB-activation. Altogether, our data further identify EGF-signalling as promising target for MM-therapy. More... »

PAGES

7180

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1209699

DOI

http://dx.doi.org/10.1038/sj.onc.1209699

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043349412

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16732320


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