Lymphoma cell adhesion-induced expression of B cell-activating factor of the TNF family in bone marrow stromal cells protects non-Hodgkin's B lymphoma cells from apoptosis

被引：53

作者：

Lwin, T. ^{[1
,2
]}

Crespo, L. A. ^{[1
,2
]}

Wu, A. ^{[1
,2
]}

Dessureault, S. ^{[1
,2
]}

Shu, H. B.

Moscinski, L. C. ^{[1
,2
]}

Sotomayor, E. ^{[1
,2
]}

Dalton, W. S. ^{[1
,2
]}

Tao, J. ^{[1
,2
]}

机构：

[1] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Oncol Sci, Tampa, FL 33613 USA

[2] Univ S Florida, H Lee Moffitt Canc Ctr, Expt Therapeut Program, Tampa, FL 33613 USA

来源：

LEUKEMIA | 2009年 / 23卷 / 01期

关键词：

non-Hodgkin's lymphoma; drug resistance; adhesion; BAFF; bone marrow stroma; NF-KAPPA-B; MYELOMA CELLS; AUTOIMMUNE-DISEASE; MULTIPLE-MYELOMA; DRUG-RESISTANCE; BAFF-R; RECEPTOR; APRIL; BLYS; BCMA;

D O I：

10.1038/leu.2008.266

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This study explores whether lymphoma cell adhesion-induced B cell-activating factor (BAFF) expression in bone marrow stromal cells (BMSCs) protects B lymphoma cells from apoptosis. We first showed protection of lymphoma cells from apoptosis by conditioned medium of a stromal cell-lymphoma cell coculture, either spontaneous or induced by mitoxantrone, implying a role for soluble factor(s) in lymphoma cell survival. Addition of BAFF counteracted mitoxantrone-induced apoptosis and elicited a reduction in spontaneous apoptosis in primary lymphomas, suggesting a role of BAFF in sustaining B-cell survival. Abundant BAFF was detected in the BMSC cell line (HS-5) and primary BMSCs by flow cytometry, RT-PCR and immunoblotting. BAFF levels were 20- to 200-fold higher in BMSCs than in lymphoma cells, and lymphoma cell adhesion to BMSCs augmented BAFF secretion twofold through upregulation of BAFF gene expression. Finally, neutralization of BAFF by TACI-Ig or depletion of BAFF by small hairpin RNA (shRNA) in BMSCs significantly enhanced lymphoma cell response to chemotherapy and overcame stroma-mediated drug resistance, suggesting that lymphoma cells use BMSC-derived BAFF as a survival factor. These findings support the hypothesis that lymphoma cells interact with BMSCs, resulting in stromal niches with high BAFF concentration, and identify BMSC-derived BAFF as a functional determinant for B lymphoma cell survival in the bone marrow environment.

引用

页码：170 / 177

页数：8

共 27 条

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