N-Cadherin in Neuroblastoma Disease: Expression and Clinical Significance

One of the first and most important steps in the metastatic cascade is the loss of cell-cell and cell-matrix interactions. N-cadherin, a crucial mediator of homotypic and heterotypic cell-cell interactions, might play a central role in the metastasis of neuroblastoma (NB), a solid tumor of neuroectodermal origin. Using Reverse Transcription Quantitative PCR (RT-qPCR), Western blot, immunocytochemistry and Tissue MicroArrays (TMA) we demonstrate the expression of N-cadherin in neuroblastoma tumors and cell lines. All neuroblastic tumors (n = 356) and cell lines (n = 10) expressed various levels of the adhesion protein. The N-cadherin mRNA expression was significantly lower in tumor samples from patients suffering metastatic disease. Treatment of NB cell lines with the N-cadherin blocking peptide ADH-1 (Exherin, Adherex Technologies Inc.), strongly inhibited tumor cell proliferation in vitro by inducing apoptosis. Our results suggest that N-cadherin signaling may play a role in neuroblastoma disease, marking involvement of metastasis and determining neuroblastoma cell viability.

肿瘤转移级联反应中首要且关键的步骤之一，便是细胞间与细胞-基质相互作用的丧失。N-钙黏蛋白（N-cadherin）是同型与异型细胞间相互作用的关键介导因子，可能在神经母细胞瘤（neuroblastoma, NB）——一种起源于神经外胚层的实体瘤——的转移过程中发挥核心作用。本研究通过逆转录定量聚合酶链反应（Reverse Transcription Quantitative PCR, RT-qPCR）、蛋白质印迹（Western blot）、免疫细胞化学及组织微阵列（Tissue MicroArrays, TMA）技术，证实了N-钙黏蛋白在神经母细胞瘤组织与细胞系中的表达情况。本次研究纳入的356份神经母细胞瘤组织样本与10株细胞系，均表达不同水平的该黏附蛋白。伴转移患者的肿瘤样本中，N-钙黏蛋白的mRNA表达水平显著降低。采用N-钙黏蛋白阻断肽ADH-1（Exherin，Adherex Technologies公司）处理神经母细胞瘤细胞系，可通过诱导细胞凋亡在体外显著抑制肿瘤细胞增殖。本研究结果表明，N-钙黏蛋白信号通路可能在神经母细胞瘤的发生发展中发挥作用，其与肿瘤转移密切相关，并可调控神经母细胞瘤细胞的存活能力。