BAFF is involved in macrophage-induced bortezomib resistance in myeloma

Chen, Jing; He, Donghua; Chen, Qingxiao; Guo, Xing; Yang, Li; Lin, Xuanru; Li, Yang; Wu, Wenjun; Yang, Yang; He, Jingsong; Zhang, Enfan; Yi, Qing; Zhang, Cai

doi:10.1038/cddis.2017.533

Cited by 22 publications

(19 citation statements)

References 43 publications

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“…The progressive effects of macrophages and fibroblasts on tumor growth are associated with the release of growth factors and anti-inflammatory mediators, their promotion of cancer invasiveness by releasing matrix degradation enzymes, and their involvement in the recruitment of suppressive cells, including T regulatory cells to the tumor side (31,32). Both aforementioned cell subsets have been shown to produce high levels of BAFF and APRIL; however, the effects of both ligands on the activation and biological function of tumor-infiltrating macrophages and tumor-associated fibroblasts remain elusive (18,24,(33)(34)(35). BAFF via direct interaction with TACI may therefore induce monocyte maturation towards macrophages and, thus, contribute to tumor progression.…”

Section: Discussionmentioning

confidence: 99%

The effects of BAFF and APRIL signaling on non‑small cell lung cancer cell proliferation and invasiveness

et al. 2021

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Lung cancer represents the most common type of human malignancy and is the main cause of cancer-associated mortality worldwide. To improve the effectiveness of treatment strategies, a better understanding of the mechanisms of cancer progression and invasiveness is required. Recently, B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), two relatively newly described cytokines belonging to the tumor necrosis factor superfamily, have been shown to play a role in cancer progression. However, at present, the effects of both cytokines on lung cancer cells remain unclear. The present study aimed therefore to understand the direct effects of BAFF and APRIL on non-small cell lung cancer (NSCLC) progression. To do so, reverse transcription quantitative PCR and western blotting were used to evaluate whether A549 and H2030 NSCLC cells express receptors for both BAFF and APRIL. The results demonstrated that both investigated cell lines expressed BAFF-R (receptor specific to BAFF only) and transmembrane activator and CAML interactor (TACI; shared receptor for both cytokines). In addition, functional experiments were performed to determine the effects of BAFF and APRIL stimulation on cancer cell viability. The results demonstrated no direct effects of BAFF and APRIL on NSCLC cell proliferation and invasiveness. In summary, the present study demonstrated that NSCLC cells possess the ability to respond directly to both BAFF and APRIL. However, activation of BAFF-R and TACI signaling in cancer cells did not increase the proliferative capacity and invasiveness. Further investigation is thus required to better understand the role of BAFF and APRIL on the progression of NSCLC.

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Section: Discussionmentioning

confidence: 99%

The effects of BAFF and APRIL signaling on non‑small cell lung cancer cell proliferation and invasiveness

et al. 2021

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“…Extensive new research has confirmed NF-κB signaling as critical in bortezomib resistance in MM cells ( 16 ). B-cell activating factor (BAFF), a cytokine in the TNF ligand family, is another important molecule shown to induce PI-resistance in MM cells ( 42 ). BAFF can drive macrophage-mediated PI-resistance and suppress caspase activation in MM cells through activation of Src, Erk1/2, Akt, and NF-κB signaling ( 42 ).…”

Section: Soluble Factor-mediated Drug Resistancementioning

confidence: 99%

“…B-cell activating factor (BAFF), a cytokine in the TNF ligand family, is another important molecule shown to induce PI-resistance in MM cells ( 42 ). BAFF can drive macrophage-mediated PI-resistance and suppress caspase activation in MM cells through activation of Src, Erk1/2, Akt, and NF-κB signaling ( 42 ). Recent work from Qin et al has shown that anti-BAFF-R antibody therapies had remarkable single-agent antitumor effects and induced potent antibody-dependent cellular cytotoxicity (ADCC) against multiple subtypes of human lymphoma and leukemia ( 16 ); we propose these may be useful in MM as well.…”

Section: Soluble Factor-mediated Drug Resistancementioning

confidence: 99%

Soluble and Cell–Cell-Mediated Drivers of Proteasome Inhibitor Resistance in Multiple Myeloma

Farrell

Reagan

2018

Front. Endocrinol.

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It is becoming clear that myeloma cell-induced disruption of the highly organized bone marrow components (both cellular and extracellular) results in destruction of the marrow and support for multiple myeloma (MM) cell proliferation, survival, migration, and drug resistance. Since the first phase I clinical trial on bortezomib was published 15 years ago, proteasome inhibitors (PIs) have become increasingly common for treatment of MM and are currently an essential part of any anti-myeloma combination therapy. PIs, either the first generation (bortezomib), second generation (carfilzomib) or oral agent (ixazomib), all take advantage of the heavy reliance of myeloma cells on the 26S proteasome for their degradation of excessive or misfolded proteins. Inhibiting the proteasome can create a crisis specifically for myeloma cells due to their rapid production of immunoglobulins. PIs have relatively few side effects and can be very effective, especially in combination therapy. If PI resistance can be overcome, these drugs may prove even more useful to a greater range of patients. Both soluble and insoluble (contact mediated) signals drive PI-resistance via activation of various intracellular signaling pathways. This review discusses the currently known mechanisms of non-autonomous (microenvironment dependent) mechanisms of PI resistance in myeloma cells. We also introduce briefly cell-autonomous and stress-mediated mechanisms of PI resistance. Our goal is to help researchers design better ways to study and overcome PI resistance, to ultimately design better combination therapies.

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“…MM-MΦs exhibit greater proliferation, resulting in elevated MM-MΦs levels in MM tumor bed 5 . Additionally, relative to regular MΦs, MM-MΦs confer MM cells with higher protection from chemotherapeutic agents 6 – 9 . Past studies indicate that MM-MΦs promote angiogenesis in MM BM 10 .…”

Section: Introductionmentioning

confidence: 99%

BMI1 regulates multiple myeloma-associated macrophage’s pro-myeloma functions

et al. 2021

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Multiple myeloma (MM) is an aggressive malignancy characterized by terminally differentiated plasma cells accumulation in the bone marrow (BM). MM BM exhibits elevated MΦs (macrophages) numbers relative to healthy BM. Current evidence indicates that MM-MΦs (MM-associated macrophages) have pro-myeloma functions, and BM MM-MΦs numbers negatively correlate with patient survival. Here, we found that BMI1, a polycomb-group protein, modulates the pro-myeloma functions of MM-MΦs, which expressed higher BMI1 levels relative to normal MΦs. In the MM tumor microenvironment, hedgehog signaling in MΦs was activated by MM-derived sonic hedgehog, and BMI1 transcription subsequently activated by c-Myc. Relative to wild-type MM-MΦs, BMI1-KO (BMI1 knockout) MM-MΦs from BM cells of BMI1-KO mice exhibited reduced proliferation and suppressed expression of angiogenic factors. Additionally, BMI1-KO MM-MΦs lost their ability to protect MM cells from chemotherapy-induced cell death. In vivo analysis showed that relative to wild-type MM-MΦs, BMI1-KO MM-MΦs lost their pro-myeloma effects. Together, our data show that BMI1 mediates the pro-myeloma functions of MM-MΦs.

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BAFF is involved in macrophage-induced bortezomib resistance in myeloma

Cited by 22 publications

References 43 publications

The effects of BAFF and APRIL signaling on non‑small cell lung cancer cell proliferation and invasiveness

The effects of BAFF and APRIL signaling on non‑small cell lung cancer cell proliferation and invasiveness

Soluble and Cell–Cell-Mediated Drivers of Proteasome Inhibitor Resistance in Multiple Myeloma

BMI1 regulates multiple myeloma-associated macrophage’s pro-myeloma functions

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