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微管相关蛋白MAPRE2参与胰腺癌细胞的神经周围浸润。

The microtubule-associated protein MAPRE2 is involved in perineural invasion of pancreatic cancer cells.

作者信息

Abiatari Ivane, Gillen Sonja, DeOliveira Tiago, Klose Theresa, Bo Kong, Giese Nathalia A, Friess Helmut, Kleeff Jörg

机构信息

Department of General Surgery, Technische Universität München, D-81675 Munich, Germany.

出版信息

Int J Oncol. 2009 Nov;35(5):1111-6. doi: 10.3892/ijo_00000426.

Abstract

Perineural invasion of tumor cells is a characteristic feature of human pancreatic cancer. Unrevealing the molecular mechanisms that enable cancer cells to invade and grow along nerves is important for the development of novel therapeutic strategies in this disease. We have previously identified transcriptional changes in highly nerve invasive pancreatic cancer cells. Here we further analyzed one of the identified deregulated genes, MAPRE2, a microtubule-associated protein. MAPRE2 expression was significantly increased in high versus less nerve invasive pancreatic cancer cells, and changes of MAPRE2 expression resulted in altered actin distribution in these cells. MAPRE2 was predominately expressed in normal pancreatic acinar cells but absent in ductal cells. In pancreatic cancer, there was strong cytoplasmic and occasionally nuclear expression of MAPRE2 in the cancer cells themselves. Increased MAPRE2 mRNA levels in bulk pancreatic cancer tissues tended to be associated with reduced postoperative survival of pancreatic cancer patients. In conclusion, MAPRE2 is highly expressed in pancreatic cancer cells, and seems to be involved in perineural invasion. Therefore, targeting this microtubule-associated protein might be a promising approach in the therapy of pancreatic cancer.

摘要

肿瘤细胞的神经周围浸润是人类胰腺癌的一个特征性表现。揭示使癌细胞能够沿神经侵袭和生长的分子机制,对于开发针对这种疾病的新型治疗策略具有重要意义。我们之前已经确定了高神经侵袭性胰腺癌细胞中的转录变化。在此,我们进一步分析了其中一个已确定的失调基因MAPRE2,它是一种微管相关蛋白。与低神经侵袭性胰腺癌细胞相比,MAPRE2在高神经侵袭性胰腺癌细胞中的表达显著增加,并且MAPRE2表达的变化导致这些细胞中肌动蛋白分布改变。MAPRE2主要在正常胰腺腺泡细胞中表达,而在导管细胞中不存在。在胰腺癌中,癌细胞自身存在强烈的细胞质表达,偶尔也有细胞核表达。胰腺癌组织中MAPRE2 mRNA水平升高往往与胰腺癌患者术后生存率降低有关。总之,MAPRE2在胰腺癌细胞中高表达,似乎参与了神经周围浸润。因此,靶向这种微管相关蛋白可能是治疗胰腺癌的一种有前景的方法。

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