Li Pei-Pei, Feng Li-Li, Chen Na, Ge Xue-Ling, Lv Xiao, Lu Kang, Ding Mei, Yuan Dai, Wang Xin
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324, Jingwu Road, Jinan, 250012, Shandong, China.
Med Oncol. 2015 Feb;32(2):479. doi: 10.1007/s12032-014-0479-5. Epub 2015 Jan 10.
Metadherin (MTDH) is involved in aberrant proliferation, migration, and chemoresistance of tumor cells. It has been demonstrated that it can promote tumor growth by modulation multiple oncogenic signaling pathways. However, MTDH expression, significance, and related mechanism in chronic lymphocytic leukemia (CLL) are still unclear. The objective of this study was to investigate the expression of MTDH in CLL and the involvement of Wnt/β-catenin signaling pathway in MTDH effects. Overexpression of MTDH mRNAs was seen in CLL samples. MTDH expression was associated with Rai stage classification of CLL, and altered levels of β2-MG and lactate dehydrogenase in serum samples from patients. Overexpression of MTDH protein was seen in 87 % of CLL samples. Specific siRNAs inhibited MEC-1 cell growth and enhanced cell apoptosis (P < 0.05). Inhibition of MTDH expression resulted in decreased expression levels of lymphoid enhancer-binding factor 1 (LEF-1), and its downstream target genes c-myc and cyclin D1. And there was a strong correlation between MTDH and LEF-1 protein expression in 14 patients with CLL. The results demonstrate that MTDH is specifically expressed in B cell of CLL and exert a preservative role through activation of Wnt signaling pathway. Our findings indicated that MTDH may be a potential therapeutic target of CLL.
黏附素（MTDH）参与肿瘤细胞的异常增殖、迁移和化疗耐药。已证实它可通过调节多种致癌信号通路促进肿瘤生长。然而，MTDH在慢性淋巴细胞白血病（CLL）中的表达、意义及相关机制仍不清楚。本研究的目的是探讨MTDH在CLL中的表达以及Wnt/β-连环蛋白信号通路在MTDH作用中的参与情况。在CLL样本中可见MTDH mRNA的过表达。MTDH表达与CLL的Rai分期分类相关，且与患者血清样本中β2-微球蛋白和乳酸脱氢酶水平的改变有关。在87%的CLL样本中可见MTDH蛋白的过表达。特异性小干扰RNA抑制MEC-1细胞生长并增强细胞凋亡（P<0.05）。抑制MTDH表达导致淋巴样增强子结合因子1（LEF-1）及其下游靶基因c-myc和细胞周期蛋白D1的表达水平降低。在14例CLL患者中，MTDH与LEF-1蛋白表达之间存在强相关性。结果表明，MTDH在CLL的B细胞中特异性表达，并通过激活Wnt信号通路发挥保护作用。我们的研究结果表明，MTDH可能是CLL的一个潜在治疗靶点。
