Expression of a soluble decoy receptor 3 in patients with diffuse large B-cell lymphoma predicts clinical outcome

Expression of a soluble decoy receptor 3 in patients with diffuse large B-cell lymphoma predicts clinical outcome
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DOI:
10.3892/ijo_00000039
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发表时间:
2008-09-01
影响因子:
5.2
通讯作者:
Yang, Muh-Hwa
Yang, Muh-Hwa
中科院分区:
医学2区
文献类型:
--
作者:
Chang, Peter Mu-Hsin;Chen, Po-Min;Yang, Muh-Hwa

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可溶性诱饵受体3(DcR 3)是TNF受体超家族的成员。它被认为是从肿瘤细胞释放的诱饵受体,通过中和FasL、LIGHT和TL 1A的细胞毒性和免疫调节作用来逃避宿主免疫应答。已经在几种人类恶性肿瘤中观察到DcR 3的过表达;然而,关于DcR 3在非霍奇金淋巴瘤中的长袍,特别是对于B细胞起源的作用,目前仅有有限的信息。在本研究中,通过RT-PCR和免疫组织化学(IHC)分析了DcR 3在一组淋巴瘤细胞系(包括T细胞和B细胞淋巴瘤)中的表达谱。结果表明,DcR 3在大多数T细胞淋巴瘤细胞中呈高表达,与以往报道一致。有趣的是,在B细胞淋巴瘤细胞系和弥漫性大B细胞淋巴瘤(DLBCL)患者中也检测到DcR 3的过表达。DcR 3过表达与DLBCL患者的预后较差相关(p=0.05)。体外研究表明,DcR 3的中和增加了阿霉素介导的两种B细胞淋巴瘤细胞系的凋亡百分比,这表明DcR 3介导的B细胞淋巴瘤化疗耐药性的可能性。我们认为DcR 3过表达与DLBCL预后不良有关,其可能机制可能是通过增加淋巴瘤细胞的化疗耐药性。
The soluble decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily. It is regarded as a decoy receptor released from tumor cells to escape host immune response by neutralizing the cytotoxic and immunomodulatory effects of FasL, LIGHT and TL1A. Overexpression of DcR3 has been observed in several human malignancies; however., only limited information exists on the robe of DcR3 in non-Hodgkin lymphoma especially for B-cell origin. In the current study, the expression profile of DcR3 was analyzed by RT-PCR and immunohistochemistry (IHC) in a set of lymphoma cell lines including T-cell and B-cell lymphomas. The result demonstrated that overexpression of DcR3 was detected in most T-cell lymphoma cells, which was consistent with previous reports. Interestingly, overexpression of DcR3 was also detected both in the B-cell lymphoma cell lines and diffuse large B cell lymphoma (DLBCL) patients. DcR3 overexpression was associated with a worse prognosis in DLBCL patients (p=0.05). An in vitro study showed that neutralization of DcR3 increased the percentage of doxorubicin-mediated apoptosis in two B-cell lymphoma cell lines, which indicated the possibility of DcR3 mediated chemo-resistance in B-cell lymphomas. We suggest that overexpression of DcR3 is associated with a worse prognosis in DLBCL and the possible mechanism may act through the increase of chemo-resistance of lymphoma cells.