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APRIL and TACI interact with syndecan‐1 on the surface of multiple myeloma cells to form an essential survival loop
Author(s) -
Moreaux Jérôme,
Sprynski AnneCatherine,
Dillon Stacey R.,
Mahtouk Karène,
Jourdan Michel,
Ythier Arnaud,
Moine Philippe,
Robert Nicolas,
Jourdan Eric,
Rossi Jean François,
Klein Bernard
Publication year - 2009
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2009.01262.x
Subject(s) - b cell activating factor , syndecan 1 , receptor , biology , microbiology and biotechnology , cancer research , b cell , cell , immunology , antibody , biochemistry
BLyS and APRIL share two receptors – transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B‐cell maturation antigen (BCMA) – and BLyS binds to a third receptor, BAFF‐R. We previously reported that TACI gene expression is a good indicator of a BLyS‐binding receptor in human multiple myeloma cell lines (HMCLs), unlike BCMA, which is expressed by all HMCLs or BAFF‐R which is typically not expressed by late‐stage B cells. We hypothesised a link between APRIL and TACI through syndecan‐1, similar to the situation reported for FGF and FGFR. We observed very strong binding of APRIL, but not BLyS, at the surface of all syndecan‐1 + HMCLs and primary multiple myeloma cells (MMC). All syndecan‐1 + HMCLs and MMC could also bind TACI‐Fc, but not BCMA‐Fc or BAFF‐R‐Fc molecules. Binding of APRIL or TACI‐Fc was abrogated by heparin or cell pretreatment with heparitinase, which cleaves heparan sulfate chains. The growth factor activity of APRIL on MMC was also inhibited by heparin. Our data identify syndecan‐1 as a co‐receptor for APRIL and TACI at the cell surface of MMC, promoting the activation of an APRIL/TACI pathway that induces survival and proliferation in MMC.