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首页> 外文期刊>Cell communication & adhesion >Connexin Over-Expression Differentially Suppresses Glioma Growth and Contributes to the Bystander Effect Following HSV-Thymidine Kinase Gene Therapy
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Connexin Over-Expression Differentially Suppresses Glioma Growth and Contributes to the Bystander Effect Following HSV-Thymidine Kinase Gene Therapy

机译：连接蛋白过表达差异抑制HSV-胸苷激酶基因治疗后胶质瘤的生长，并有助于旁观者的作用。

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摘要

Neoplastic transformation is frequently associated with a loss of gap junctional intercellular communication and reduced expression of connexins. The introduction of connexin genes into tumor cells reverses the proliferative characteristics of such cells. However, there is very little comparative information on the effects of different connexins on cancer cell growth. We hypothesized that Cx26, Cx32, or Cx43 would display differential growth suppression of C6 glioma cells and uniquely modulate the bystander effect following transduction of C6 cells with HSVtk followed by suicide gene therapy. The bystander phenomenon is the death of a greater number of tumor cells than are expressing the HSVtk gene, presumably due to the passage of toxic molecules through gap junction channels. To test this hypothesis, we used retroviral vectors to infect C6 glioma cells producing connexin-expressing and HSVtk-expressing cell lines. All three connexin-expressing cell lines grew significantly slower than GFP-infected or native C6 cells. Cx32 and Cx26 were significantly more effective at mediating the bystander effect in cocultures of C6-connexin cells with C6-HSVtk cells. These studies indicate that connexins have unique properties that contribute to their tumor suppressive function.
机译：肿瘤转化通常与间隙连接细胞间通讯的丧失和连接蛋白的表达降低有关。将连接蛋白基因导入肿瘤细胞可逆转此类细胞的增殖特性。但是，关于不同连接蛋白对癌细胞生长的影响的比较信息很少。我们假设Cx26，Cx32或Cx43将显示出对C6胶质瘤细胞的不同生长抑制作用，并在通过HSVtk转导C6细胞后继之以自杀基因治疗后，独特地调节旁观者效应。旁观者现象是死亡的肿瘤细胞数量多于表达HSVtk基因的肿瘤细胞，大概是由于有毒分子通过间隙连接通道的传递。为了验证这一假设，我们使用了逆转录病毒载体感染产生连接蛋白表达和HSVtk表达细胞系的C6胶质瘤细胞。所有这三种表达连接蛋白的细胞系的生长均明显慢于GFP感染或天然C6细胞。 Cx32和Cx26在介导C6-连接蛋白细胞与C6-HSVtk细胞共培养的旁观者效应方面更有效。这些研究表明连接蛋白具有独特的特性，有助于其抑制肿瘤的功能。

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