APRIL and TACI interact with syndecan-1 on the surface of multiple myeloma cells to form an essential survival loop
APRIL and TACI interact with syndecan-1 on the surface of multiple myeloma cells to form an essential survival loop
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DOI：
10.1111/j.1600-0609.2009.01262.x
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发表时间：
2009-08-01
影响因子：
3.1
通讯作者：
Klein, Bernard
中科院分区：
文献类型：
--
作者：
Moreaux, Jerome;Sprynski, Anne-Catherine;Klein, Bernard
BLyS和APRIL共有两种受体-跨膜激活剂和钙调节剂和亲环蛋白配体相互作用物（TACI）和B细胞成熟抗原（BCMA）-BLyS结合第三种受体BAFF-R。我们先前报道了TACI基因表达是人类多发性骨髓瘤细胞系（HMCL）中BLyS结合受体的良好指标，不像BCMA，其由所有HMCL表达或BAFF-R，其通常不由晚期B细胞表达。我们假设APRIL和TACI之间通过syndecan-1的联系，类似于FGF和FGFR的情况。我们观察到APRIL在所有多配体蛋白聚糖-1（+）HMCL和原发性多发性骨髓瘤细胞（MMC）的表面具有非常强的结合，但BLyS没有。所有syndecan-1（+）HMCL和MMC也可结合TACI-Fc，但不结合BCMA-Fc或BAFF-R-Fc分子。APRIL或泰爱Fc的结合通过肝素或用肝素酶（其切割硫酸乙酰肝素链）预处理细胞而被废除。APRIL对MMC的生长因子活性也被肝素抑制。我们的数据确定syndecan-1作为APRIL和TACI在MMC细胞表面的共受体，促进APRIL/TACI通路的激活，诱导MMC中的存活和增殖。
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.