Integrin inhibitor suppresses bevacizumab-induced glioma invasion.
Integrin inhibitor suppresses bevacizumab-induced glioma invasion.
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整联蛋白抑制剂抑制贝伐单抗诱导的神经胶质瘤侵袭。
DOI：
10.1016/j.tranon.2014.02.016
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发表时间：
2014-04
影响因子：
5
通讯作者：
Date, Isao
中科院分区：
文献类型：
--
作者：
Ishida, Joji;Onishi, Manabu;Kurozumi, Kazuhiko;Ichikawa, Tomotsugu;Fujii, Kentaro;Shimazu, Yosuke;Oka, Tetsuo;Date, Isao
已知胶质母细胞瘤分泌高水平的血管内皮生长因子（VEGF），并且使用贝伐单抗（VEGF的单克隆抗体）的临床研究已经证明在胶质母细胞瘤患者中具有令人信服的治疗益处。然而，也有报道其诱导侵袭性增殖。我们研究了整合素抑制剂西仑吉肽对贝伐珠单抗诱导的胶质瘤侵袭性变化的影响。将U87ΔEGFR细胞立体定向注射到裸鼠或大鼠的脑中。肿瘤植入后5天，每周3次腹腔内给予西仑吉肽和贝伐单抗。在肿瘤植入后18天，取出脑组织并进行组织病理学观察。接下来，使用微阵列分析比较贝伐单抗和西仑吉肽组合组与贝伐单抗单一治疗组。贝伐单抗治疗导致增加的细胞侵袭，尽管减少血管生成。当用贝伐单抗和西仑吉肽联合治疗大鼠时，肿瘤浸润的深度显著小于仅用贝伐单抗。通路分析证实了联合组中侵袭相关基因如整合素介导的细胞粘附通路的抑制。这项研究表明，贝伐珠单抗与西仑吉肽联合使用发挥了其抗侵袭作用。阐明这一机制可能有助于治疗贝伐珠单抗难治性胶质瘤。
Glioblastoma is known to secrete high levels of vascular endothelial growth factor (VEGF), and clinical studies with bevacizumab, a monoclonal antibody to VEGF, have demonstrated convincing therapeutic benefits in glioblastoma patients. However, its induction of invasive proliferation has also been reported. We examined the effects of treatment with cilengitide, an integrin inhibitor, on bevacizumab-induced invasive changes in glioma. U87ΔEGFR cells were stereotactically injected into the brain of nude mice or rats. Five days after tumor implantation, cilengitide and bevacizumab were administered intraperitoneally three times a week. At 18 days after tumor implantation, the brains were removed and observed histopathologically. Next, the bevacizumab and cilengitide combination group was compared to the bevacizumab monotherapy group using microarray analysis. Bevacizumab treatment led to increased cell invasion in spite of decreased angiogenesis. When the rats were treated with a combination of bevacizumab and cilengitide, the depth of tumor invasion was significantly less than with only bevacizumab. Pathway analysis demonstrated the inhibition of invasion-associated genes such as the integrin-mediated cell adhesion pathway in the combination group. This study showed that the combination of bevacizumab with cilengitide exerted its anti-invasive effect. The elucidation of this mechanism might contribute to the treatment of bevacizumab-refractory glioma.
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影响因子：
158.5
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