Semaphorin-3D and semaphorin-3E inhibit the development of tumors from glioblastoma cells implanted in the cortex of the brain.
Semaphorin-3D and semaphorin-3E inhibit the development of tumors from glioblastoma cells implanted in the cortex of the brain.
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DOI：
10.1371/journal.pone.0042912
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Neufeld G
中科院分区：
文献类型：
--
作者：
Sabag AD;Bode J;Fink D;Kigel B;Kugler W;Neufeld G
3 类信号蛋白是分泌型轴突导向因子。其中一些信号蛋白最近被定性为肿瘤进展的抑制剂。为了确定 3 类信号蛋白是否可用于抑制多形性胶质母细胞瘤肿瘤的发展，我们在 U87MG 胶质母细胞瘤细胞中表达重组 sema-3A、3B、3D、3E、3F 或 3G。表达 Sema3A 和 sema3B 的细胞持续收缩并改变形状，而表达其他信号蛋白的细胞则不然。 Sema3A 和 sema3F 与包括 sema3B 在内的其他信号蛋白不同，因为它们还抑制细胞增殖和软琼脂集落的形成。除 sema3G 和 sema3B 外，U87MG 细胞中这些信号蛋白的表达显着抑制皮下植入细胞的肿瘤发展。将表达每种 3 类信号蛋白的 U87MG 细胞植入小鼠大脑皮层后，也观察到对肿瘤发展的强烈抑制。 Sema3D和sema3E表现出最强的抑制作用，它们在植入小鼠大脑的U373MG或U87MG胶质母细胞瘤细胞中的表达使小鼠的存活时间延长了两倍以上。此外，大多数在实验结束前死亡的小鼠没有发展出可检测到的肿瘤，并且许多小鼠存活到实验结束。我们在这里使用的大多数信号蛋白（sema3D 除外）之前都被描述为血管生成抑制剂。我们的结果表明 sema3D 还起到血管生成抑制剂的作用，并表明抗肿瘤作用主要是由于抑制肿瘤血管生成。这些结果表明 sema3D 和 sema3E 等 3 类信号蛋白或许可用于治疗胶质母细胞瘤患者。
Class-3 semaphorins are secreted axon guidance factors. Some of these semaphorins have recently been characterized as suppressors of tumor progression. To determine if class-3 semaphorins can be used to inhibit the development of glioblastoma-multiforme tumors, we expressed recombinant sema-3A, 3B, 3D, 3E, 3F or 3G in U87MG glioblastoma cells. Sema3A and sema3B expressing cells contracted and changed shape persistently while cells expressing other semaphorins did not. Sema3A and sema3F differed from other semaphorins including sema3B as they also inhibited the proliferation of the cells and the formation of soft agar colonies. With the exception of sema3G and sema3B, expression of these semaphorins in U87MG cells inhibited significantly tumor development from subcutaneously implanted cells. Strong inhibition of tumor development was also observed following implantation of U87MG cells expressing each of the class-3 semaphorins in the cortex of mouse brains. Sema3D and sema3E displayed the strongest inhibitory effects and their expression in U373MG or in U87MG glioblastoma cells implanted in the brains of mice prolonged the survival of the mice by more then two folds. Furthermore, most of the mice that died prior to the end of the experiment did not develop detectable tumors and many of the mice survived to the end of the experiment. Most of the semaphorins that we have used here with the exception of sema3D were characterized previously as inhibitors of angiogenesis. Our results indicate that sema3D also functions as an inhibitor of angiogenesis and suggest that the anti-tumorigenic effects are due primarily to inhibition of tumor angiogenesis. These results indicate that class-3 semaphorins such as sema3D and sema3E could perhaps be used to treat glioblastoma patients.
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影响因子：
8
作者：
Bagci, T.;Wu, J. K.;Jay, D. G.
通讯作者：
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影响因子：
20.3
作者：
Sulpice, Eric;Plouet, Jean;Merkulova-Rainon, Tatyana
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影响因子：
11.2
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Neufeld, G
影响因子：
20.3
作者：
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影响因子：
8.4
作者：
Vermeulen, PB;Gasparini, G;Dirix, LY
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