Migration of mouse-induced pluripotent stem cells to glioma-conditioned medium is mediated by tumor-associated specific growth factors
Migration of mouse-induced pluripotent stem cells to glioma-conditioned medium is mediated by tumor-associated specific growth factors
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DOI：
10.3892/ol.2011.234
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发表时间：
2011-03-01
期刊：
影响因子：
2.9
通讯作者：
Namba, Hiroki
中科院分区：
文献类型：
--
作者：
Koizumi, Shinichiro;Gu, Chunyu;Namba, Hiroki
神经干细胞和间充质干细胞对恶性胶质瘤具有广泛的趋向性。采用Matrigel侵袭实验检测诱导多能干细胞(IPS)的肿瘤趋向性。小鼠iPS细胞对6种啮齿动物和人脑胶质瘤细胞系制备的条件培养液表现出明显的趋向性，这种趋向性可被恶性胶质瘤分泌的四种主要肿瘤相关生长因子[干细胞c，11因子(SCF)，血小板衍生生长因子BB(PDGF-BB)，基质衍生因子-1α(SDF-1α)和血管内皮生长因子(VEGF)]的中和抗体部分阻断。这些生长因子在0.1~100 ng/ml范围内呈浓度依赖性地增强iPS细胞的趋向性，逆转录聚合酶链式反应检测到这些生长因子受体(c-Kit、ICAM-1、CXCR4和VEGFR2)在小鼠iPS细胞中的表达较小鼠成纤维细胞显著上调。结果表明，该细胞能分泌特异性生长因子。从胶质瘤中强烈吸引iPS细胞。因此，利用iPS细胞作为载体运送抗肿瘤药物的基因治疗是治疗深度浸润性脑胶质瘤的新策略。
Neural and mesenchymal stem cells have extensive tropism for malignant glioma. The tumor tropism of induced pluripotent stem (iPS) cells was tested using the Matrigel invasion assay. Mouse iPS cells showed a significant tropism to the conditioned media prepared from six rodent and human glioma cell lines and this tropism to the glioma conditioned media was partially blocked by the neutralizing antibodies for four major tumor-associated growth factors [stem c,11 factor (SCF), platelet-derived growth factor BB (PDGF-BB), stromal-derived factor-1 alpha (SDF-1 alpha) and vascular endothelial growth factor (VEGF)], which are secreted from the malignant gliomas. The tropism of the iPS cells was enhanced by the growth factors in a concentration-dependent manner from 0.1 to 100 ng/ml. The receptors for those growth factors (c-Kit, ICAM-1, CXCR4 and VEGFR2), measured by reverse transcriptase-polymerase chain reaction, were highly up-regulated in the mouse iPS cells compared to the mouse fibroblasts. The results showed that the specific growth factors secreted. from the gliomas strongly attracted the iPS cells. Therefore, gene therapies using iPS cells as vectors to deliver anti-tumor agents are novel strategies for the treatment of malignant gliomas that deeply infiltrate the brain.