Chang Peter Mu-Hsin, Chen Po-Min, Hsieh Shie-Liang, Tzeng Cheng-Hwai, Liu Jin-Hwang, Chiou Tzeon-Jye, Wang Wei-Shu, Yen Chueh-Chuan, Gau Jyh-Pyng, Yang Muh-Hwa
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R O C.
Int J Oncol. 2008 Sep;33(3):549-54.
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 role 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.
可溶性诱骗受体3（DcR3）是肿瘤坏死因子受体超家族的成员。它被认为是一种从肿瘤细胞释放的诱骗受体，通过中和FasL、LIGHT和TL1A的细胞毒性和免疫调节作用来逃避宿主免疫反应。在几种人类恶性肿瘤中均观察到DcR3的过表达；然而，关于DcR3在非霍奇金淋巴瘤尤其是B细胞起源淋巴瘤中的作用，目前仅有有限的信息。在本研究中，通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学（IHC）分析了一组包括T细胞和B细胞淋巴瘤的淋巴瘤细胞系中DcR3的表达谱。结果表明，在大多数T细胞淋巴瘤细胞中检测到DcR3过表达，这与先前的报道一致。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DcR3过表达。DcR3过表达与DLBCL患者的预后较差相关（p=0.05）。一项体外研究表明，中和DcR3可增加两种B细胞淋巴瘤细胞系中阿霉素介导的凋亡百分比，这表明DcR3可能介导B细胞淋巴瘤的化疗耐药性。我们认为，DcR3过表达与DLBCL患者的预后较差相关，其可能机制可能是通过增加淋巴瘤细胞的化疗耐药性来实现的。
