Oncolytic bovine herpesvirus type 1 infects and kills breast tumor cells and breast cancer-initiating cells irrespective of tumor subtype
Oncolytic bovine herpesvirus type 1 infects and kills breast tumor cells and breast cancer-initiating cells irrespective of tumor subtype
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DOI：
10.1038/cgt.2013.18
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发表时间：
2013-05-01
影响因子：
6.4
通讯作者：
Mossman, K. L.
中科院分区：
文献类型：
--
作者：
Cuddington, B. P.;Dyer, A. L.;Mossman, K. L.
溶瘤病毒是有吸引力的癌症治疗剂，因为它们独特的肿瘤细胞靶向机制和没有与当前治疗相关的毒副作用。牛疱疹病毒1型（BHV-1）是一种特异性疱疹病毒，不能在正常人细胞中诱导细胞病变效应，但能够感染和杀死多种永生化和转化的人细胞类型，包括来自管腔、基底A和基底B亚型的人乳腺肿瘤细胞系，代表多种受体表达谱。BHV-1能够在体细胞和侧群细胞中启动复制并杀死它们，后者具有增强的肿瘤启动能力。尽管缺乏生产性感染或细胞毒性因子的分泌，但BHV-1感染降低了低感染复数后长期培养中的细胞活力。此外，BHV-1感染的MCF 7细胞在体内形成肿瘤的能力显著降低。总体而言，这些研究表明，溶瘤BHV-1通过一种新的机制靶向大量乳腺癌细胞和来自管腔和基底亚型的癌症起始细胞，该机制不依赖于细胞受体表达状态。
Oncolytic viruses are attractive cancer therapeutics because of their unique mechanisms of tumor cell targeting and the absence of toxic side effects associated with current treatments. Bovine herpesvirus type 1 (BHV-1) is a species-specific herpesvirus that fails to induce cytopathic effects in normal human cells, but is capable of infecting and killing a variety of immortalized and transformed human cell types, including human breast tumor cell lines from luminal, basal A and basal B subtypes, representing a variety of receptor expression profiles. BHV-1 is capable of initiating replication in and killing both bulk and side population cells, the latter of which have enhanced tumor-initiating capacity. Despite the lack of a productive infection or secretion of cytotoxic factors, BHV-1 infection decreases cellular viability in long-term culture following low multiplicity of infection. Moreover, BHV-1-infected MCF7 cells are significantly diminished in their capacity to form tumors in vivo. Overall, these studies suggest that oncolytic BHV-1 targets bulk breast cancer cells and cancer-initiating cells from luminal and basal subtypes by a novel mechanism that is not contingent upon cellular receptor expression status.