APRIL and TACI interact with syndecan-1 on the surface of multiple myeloma cells to form an essential survival loop

Jérôme Moreaux1, Anne-Catherine Sprynski, Stacey R Dillon

  • 1CHU Montpellier, Institute of Research in Biotherapy, Montpellier, France.

Insights

Syndecan-1 acts as a co-receptor for APRIL and TACI in multiple myeloma cells. This interaction activates a pathway promoting cancer cell survival and proliferation.

Area of Science:

  • Hematology
  • Molecular Biology
  • Cell Biology

Background:

  • B-cell activating factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL) are key cytokines in B-cell biology.
  • Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), B-cell maturation antigen (BCMA), and BAFF receptor (BAFF-R) are receptors for BAFF and APRIL.
  • Syndecan-1 is a cell surface proteoglycan implicated in various cellular processes.

Purpose of the Study:

  • To investigate the role of syndecan-1 as a co-receptor for APRIL and TACI in human multiple myeloma cell lines (HMCLs) and primary multiple myeloma cells (MMC).
  • To elucidate the mechanism by which APRIL and TACI interact with syndecan-1 to influence myeloma cell growth.

Main Methods:

  • Binding assays using APRIL, TACI-Fc, BCMA-Fc, and BAFF-R-Fc on syndecan-1 positive (syndecan-1(+)) HMCLs and MMC.
  • Inhibition studies using heparin and heparitinase to assess the role of heparan sulfate chains.
  • Assessment of APRIL's growth factor activity on MMC.

Main Results:

  • APRIL, but not BAFF, strongly bound to the surface of syndecan-1(+) HMCLs and MMC.
  • Syndecan-1(+) HMCLs and MMC bound TACI-Fc, but not BCMA-Fc or BAFF-R-Fc.
  • Binding of APRIL and TACI-Fc was blocked by heparin and heparitinase, indicating the involvement of heparan sulfate chains.
  • Heparin inhibited APRIL's growth-promoting activity on MMC.

Conclusions:

  • Syndecan-1 functions as a co-receptor for APRIL and TACI on the surface of multiple myeloma cells.
  • The APRIL/TACI pathway, mediated by syndecan-1, promotes the survival and proliferation of multiple myeloma cells.
  • Targeting the syndecan-1/APRIL/TACI axis may offer a therapeutic strategy for multiple myeloma.

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