Bone marrow stromal cells induced activation of nuclear factor κB signaling protects non-Hodgkin’s B lymphoma cells from apoptosis

Su, Tong; Li, Jiakai; Meng, Minghui; Zhao, Sheng; Xu, Yali; Ding, Xiaofeng; Jiang, Hong; Ma, Xiaoli; Qian, Jin; Han, Wei; Sun, Lixin; Li, Xiaobin; Liu, Zuojun; Pan, Lei; Xue, Xinying

doi:10.1007/s13277-016-4860-1

Cited by 8 publications

(7 citation statements)

References 38 publications

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“…We therefore concluded that Notch pathway activation correlates with tumor cell proliferation, as shown by previous studies [34, 35]. Regarding chemoresistance, lymphoma cells cultured alone were more sensitive to lymphoma cells from the coculture system, as previous studies indicated [36]. But Notch-bearing adherent lymphoma cells did not show superiority to suspended lymphoma cells in our study.…”

Section: Discussionsupporting

confidence: 82%

“…Furthermore, cancer stem cells or the tumor-initiating cells of BCL maintain their tumorigenic potential via interplay with the TME [15, 16]. Previous studies have demonstrated that the protective effect of the TME was mediated through tumor-stroma cell interactions, especially direct cell-to-cell contact between tumor cells and stromal cells [17-19]. It is recognized that the Notch pathway is a canonical signal-transducing pathway mediating cell-to-cell communication.…”

Section: Introductionmentioning

confidence: 99%

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Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells

Lin¹,

Chen²,

Wu³

et al. 2018

Acta Haematol

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Background/Aims: Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity. Methods: We created a coculture system using human DLBCL cells and mouse bone marrow stromal cells. Proliferative capacity, drug resistance, clonogenicity, and tumorigenicity were compared in lymphoma cells from the coculture system and lymphoma cells cultured alone. Expression of Notch signaling associated genes was evaluated using real-time reverse transcriptase PCR and Western blot. Results: Lymphoma cells in the coculture system differentiated into a suspended cell group and an adherent cell group. They acquired a stronger proliferative capacity and drug resistance than lymphoma cells cultured alone, and differences existed between the adherent cell and suspended cell groups. The suspended cell group acquired the most powerful clonogenic and tumorigenic potential. However, Notch3 was exclusively expressed in the adherent lymphoma cell group and the use of N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, an inhibitor of Notch pathway, could abolish the emergence of highly aggressive lymphoma cells. Conclusion: Highly tumorigenic lymphoma cells could be generated by coculture with stromal cells, and it was dependent on Notch3 expression in the adjacent lymphoma cells through interaction with stromal cells.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells

Lin¹,

Chen²,

Wu³

et al. 2018

Acta Haematol

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“…However, accumulating evidence indicates that MSCs act as pro-tumor factors that interact with lymphoma cells and promote lymphoma growth, survival, and drug-resistance through multiple mechanisms [8, 25]. Recent studies show that hATMSCs or hBMSCs promote growth and drug-resistance in Burkitt lymphoma cells or DLBCL cells in vitro or in vivo [9, 10, 26, 27]. Here, we found that hBMSCs promoted the growth and drug-resistance of SU-DHL-2 and SU-DHL-4 cells in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

Human bone marrow-derived mesenchymal stem cells promote the growth and drug-resistance of diffuse large B-cell lymphoma by secreting IL-6 and elevating IL-17A levels

Zhong

Zhu

et al. 2019

J Exp Clin Cancer Res

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BackgroundThe drug-resistance and relapse of diffuse large B-cell lymphoma (DLBCL), which are related to mesenchymal stem cells (MSCs), have become increasingly common. However, the underlying mechanisms remain elusive.MethodsCCK 8 assay, colony formation assay, and xenograft mouse model were used to investigate the effects of hBMSCs on DLBCL growth. Immunohistochemistry, qRT-PCR, and ELISA were used to study the expressions of IL-6 and IL-17A. Flow cytometry was used to analyze Th17 cells and Treg cells expressions. Western blot analysis, microarray analysis, and bioinformatics analysis were used to analyze the pathways of IL-6 or IL-17A mediated DLBCL growth.ResultsHBMSCs promoted DLBCL growth by secreting IL-6 in vitro and in vivo and simultaneously upregulating IL-17A in vitro. IL-6 and IL-17A synergistically promoted the growth and drug-resistance of DLBCL cells by protecting them from spontaneous or drug-induced apoptosis in vitro. IL-6 or IL-17A activated the JAK2/STAT3 pathway or upregulated cyclin D2 via activation of PI3K/Akt signaling in vitro, respectively.ConclusionsThe present results indicated that hBMSCs might have a “dual effect” on promoting DLBCL progression and drug-resistance by secreting IL-6 and upregulating IL-17A. IL-6, IL-17A, p-STAT3, p-Akt or cyclin D2 may be potential molecular targets for overcoming drug-resistance in patients with relapsed or refractory DLBCL.

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“…This is similar to the interaction between BAFF and its receptors on lymphoma and normal B cells, which promotes I κ B α degradation and processes of NF- κ B2, respectively. 39 , 40 , 41 , 42 …”

Section: Discussionmentioning

confidence: 99%

BAFF is involved in macrophage-induced bortezomib resistance in myeloma

Chen

et al. 2017

Cell Death Dis

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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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Bone marrow stromal cells induced activation of nuclear factor κB signaling protects non-Hodgkin’s B lymphoma cells from apoptosis

Cited by 8 publications

References 38 publications

Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells

Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells

Human bone marrow-derived mesenchymal stem cells promote the growth and drug-resistance of diffuse large B-cell lymphoma by secreting IL-6 and elevating IL-17A levels

BAFF is involved in macrophage-induced bortezomib resistance in myeloma

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