BAFF is involved in macrophage-induced bortezomib resistance in myeloma

Cell Death & Disease
Jing ChenZhen Cai

Abstract

We aimed to characterize the role of B-cell activating factor (BAFF) in macrophage-mediated resistance of multiple myeloma (MM) cells to bortezomib (bort), and to further understand the molecular mechanisms involved in the process. First, we detected BAFF and its three receptors on myeloma cells and macrophages using the quantitative reverse transcriptase-polymerase chain reaction and flow cytometry. The secretion of BAFF was tested in patients with MM, MM cell lines, and macrophages. The ability of macrophages to protect MM cells from bort-induced apoptosis was significantly attenuated using BAFF-neutralizing antibody in the co-culture system or knocking down the expression of BAFF in macrophages with small interfering RNA. We also showed that the MM-macrophage interaction through BAFF and its receptors was primarily mediated by the activation of Src, Erk1/2, Akt, and nuclear factor kappa B signaling and the suppression of caspase activation induced by bort. Our data demonstrated that BAFF played a functional role in the macrophage-mediated resistance of MM cells to bort, suggesting that targeting BAFF may provide a basis for the molecular- and immune-targeted therapeutic approach.

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Citations

May 17, 2018·Frontiers in Endocrinology·Mariah L Farrell, Michaela R Reagan
Jan 7, 2021·Cancer Metastasis Reviews·Khatora S OppermanAndrew C W Zannettino
May 17, 2021·Cell Death & Disease·Danfeng ZhangYuhuan Zheng

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Methods Mentioned

BETA
flow cytometry
nuclear translocation
enzyme-linked immunosorbent assay
Protein Assay
electrophoresis
biopsy

Software Mentioned

FlowJo7
GraphPad Prism
POWER

Related Concepts

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Apoptosis

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