【新思路】靶向健康细胞，阻止癌症扩散

  近日，刊登在国际杂志Oncogene及Oncotarget上的研究论文中，来自英属哥伦比亚大学(University Of British Columbia)的研究人员通过对脑癌进行深入研究或可帮助开发新型疗法，来靶向作用肿瘤周围的细胞以阻断癌症发生扩散。

  研究者Christian Naus说道，我们主要对名为神经胶质瘤的恶性成年脑瘤进行研究，神经胶质瘤患者的5年平均存活率低于30%，因为目前并没有疗法在不破坏大脑功能的前体下实现对脑癌细胞的完全清除；化疗和放疗方法也不能抑制残存癌细胞的再度生长。
  这项研究中，研究者揭示了一种控制神经胶质瘤癌细胞的可替代的途径，星型细胞可以调节大脑环境产生利于大脑功能发挥的适宜条件，而研究者将癌细胞同星型细胞混合后他们发现，神经胶质瘤可以利用少许的microRNAs对星形细胞实施重编程，microRNAs可以扮演主要的调节开关，来开启或关闭一系列基因的表达。
  研究者Naus教授说道，这项研究首次提出，microRNAs可以从神经胶质瘤细胞到星型细胞中并且对星型细胞进行重编程来提供刺激肿瘤生长及扩散的最佳环境；研究者希望后期可以开发一种新型疗法短暂地修饰肿瘤周围的星型细胞以便脑癌细胞不能对星型细胞进行重编程。
  目前该研究已经被列为大型的跨学科研究，研究名为“剖析癌症：美丽与破坏之间的关联”，研究者表示，对脑癌图像的研究货可以帮助理解脑癌的发病机制，为开发靶向性的新型疗法或将带来巨大的帮助和希望。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Astrocytes promote glioma invasion via the gap junction protein connexin43.
Oncogene       doi:10.1038/onc.2015.210
Sin WC1, Aftab Q1, Bechberger JF1, Leung JH1, Chen H1, Naus CC1.
Reactive astrocytes are integral to the glioma microenvironment. Connexin43 (Cx43) is a major gap junction protein in astrocytes and its expression is enhanced significantly in glioma-associated astrocytes, especially at the peri-tumoral region. Although downregulation of Cx43-mediated intercellular communication is associated with increased malignancy in tumor cells, the role of Cx43 in stromal cells in glioma progression is not defined. Using a mouse model consisting of syngeneic intracranial implantation of GL261 glioma cells into Nestin-Cre:Cx43fl/fl mice where Cx43 was eliminated in astrocytes, we demonstrate a role of astrocytic Cx43 in the dissemination of glioma cells from the tumor core. To determine whether heterocellular communication between astrocytes and glioma cells is essential for reduced invasion in the absence of astrocytic Cx43, we abolished channel formation between glioma cells and astrocytes by either knocking down Cx43 in glioma cells with short hairpin RNA (shRNA) or overexpressing a dominant-negative channel-defective Cx43-T154A mutant in these cells. Although Cx43shRNA in glioma cells reduced invasion, expression of Cx43-T154A had no effect on glioma invasion, suggesting tumoral Cx43 may influence motility independently from its channel function. Alteration in astrocytic Cx43 function, such as by replacing the wild-type allele with a C-terminal truncated Cx43 mutant exhibiting reduced intercellular coupling, is sufficient to reduce glioma spreading into the brain parenchyma. Our results reveal a novel role of astrocytic Cx43 in the formation of an invasive niche and raise the possibility to control glioma progression by manipulating the microenvironment.

其它相关研究链接：

【1】Reduction in gap junction intercellular communication promotes glioma migration.

【2】Gap junctions modulate glioma invasion by direct transfer of microRNA.