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一种对信号淋巴细胞激活分子具有选择性抗性的麻疹病毒对肺癌细胞显示出抗肿瘤活性。

A measles virus selectively blind to signaling lymphocytic activation molecule shows anti-tumor activity against lung cancer cells.

作者信息

Fujiyuki Tomoko, Yoneda Misako, Amagai Yosuke, Obayashi Kunie, Ikeda Fusako, Shoji Koichiro, Murakami Yoshinori, Sato Hiroki, Kai Chieko

机构信息

Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.

Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.

出版信息

Oncotarget. 2015 Sep 22;6(28):24895-903. doi: 10.18632/oncotarget.4366.

Abstract

Lung cancer cells, particularly those of non-small-cell lung cancer, are known to express Nectin-4. We previously generated a recombinant measles virus that uses Nectin-4 as its receptor but cannot bind its original principal receptor, signaling lymphocyte activation molecule (SLAM). This virus (rMV-SLAMblind) infects and kills breast cancer cells in vitro and in a subcutaneous xenograft model. However, it has yet to be determined whether rMV-SLAMblind is effective against other cancer types and in other tumor models that more closely represent disease. In this study, we analyzed the anti-tumor activity of this virus towards lung cancer cells using a modified variant that encodes green fluorescent protein (rMV-EGFP-SLAMblind). We found that rMV-EGFP-SLAMblind efficiently infected nine, human, lung cancer cell lines, and its infection resulted in reduced cell viability of six cell lines. Administration of the virus into subcutaneous tumors of xenotransplanted mice suppressed tumor growth. In addition, rMV-EGFP-SLAMblind could target scattered tumor masses grown in the lungs of xenotransplanted mice. These results suggest that rMV-SLAMblind is oncolytic for lung cancer and that it represents a promising tool for the treatment of this disease.

摘要

已知肺癌细胞,尤其是非小细胞肺癌细胞会表达Nectin-4。我们之前构建了一种重组麻疹病毒,该病毒以Nectin-4作为其受体,但无法结合其原始主要受体——信号淋巴细胞激活分子(SLAM)。这种病毒(rMV-SLAMblind)在体外和皮下异种移植模型中可感染并杀死乳腺癌细胞。然而,rMV-SLAMblind对其他癌症类型以及在更能代表疾病的其他肿瘤模型中是否有效,尚待确定。在本研究中,我们使用编码绿色荧光蛋白的修饰变体(rMV-EGFP-SLAMblind)分析了该病毒对肺癌细胞的抗肿瘤活性。我们发现rMV-EGFP-SLAMblind能有效感染9种人肺癌细胞系,其感染导致6种细胞系的细胞活力降低。将该病毒接种到异种移植小鼠的皮下肿瘤中可抑制肿瘤生长。此外,rMV-EGFP-SLAMblind能够靶向异种移植小鼠肺部生长的散在肿瘤块。这些结果表明rMV-SLAMblind对肺癌具有溶瘤作用,并且它是治疗该疾病的一种有前景的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b145/4694801/d99dedfd4b71/oncotarget-06-24895-g001.jpg

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