Treatment of breast cancer stem cells with oncolytic herpes simplex virus.
Treatment of breast cancer stem cells with oncolytic herpes simplex virus.
复制标题
用溶瘤单纯疱疹病毒治疗乳腺癌干细胞
DOI：
10.1038/cgt.2012.49
复制
发表时间：
2012-10
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
作者：
最近从几种不同的实体肿瘤中分离出了癌症干细胞。在乳腺癌中，CD44+CD24−/Low群体被认为是由干细胞样细胞组成。肿瘤干细胞的鉴定为治疗学的发展提供了新的靶点。溶瘤单纯疱疹病毒(OHSV)是临床前模型中杀灭乳腺癌细胞和治疗乳腺肿瘤的有效策略。在这里，我们检测了OHSVG47Δ在杀死乳腺癌干细胞方面的效果。人乳腺癌细胞系SK-BR-3和人原代乳腺癌细胞在有利于干细胞生长的条件下进行悬浮培养。他们产生了具有癌症干细胞特性的乳房。经流式细胞仪检测，这些乳腺组织中CD44+CD24Low细胞的比例超过95%。将乳房植入BALB/c裸鼠皮下，发现其具有很强的致瘤性。G47Δ含有lacZ基因，体内外感染细胞的X-Gal染色显示病毒的复制和扩散。G47Δ在体外对CD4 4+CD2 4−/Low群体具有高度的细胞毒作用，即使在低感染复数下注射也是如此，体内G47Δ治疗与模拟治疗相比显著抑制肿瘤生长。这项研究表明，OHSV对乳腺癌干细胞是有效的，可能是治疗乳腺癌患者的一种有益的策略。
Cancer stem cells have recently been isolated from several different solid tumors. In breast cancer, the CD44+CD24−/low population is considered to comprise stem-like cells. The identification of cancer stem cells has provided new targets for the development of therapeutics. Oncolytic herpes simplex viruses (oHSVs) are an effective strategy for killing breast cancer cells and treating breast tumors in preclinical models. Here, we examined the efficacy of the oHSV G47Δ in killing breast cancer stem cells. Human breast cancer cell line SK-BR-3 and human primary breast cancer cells were cultured in suspension under conditions conducive to the growth of stem cells. They generated mammospheres, which had cancer stem cell properties. The proportion of CD44+CD24−/low cells in these mammospheres exceeded 95%, as determined by flow cytometry. The mammospheres were found to be highly tumorigenic when implanted subcutaneously in nude BALB/c mice. G47Δ contains the LacZ gene, and X-gal staining of infected cells in vitro and in vivo showed the replication and spread of the virus. G47Δ was found to be highly cytotoxic to the CD44+CD24−/low population in vitro, even when injected at low multiplicities of infection, and G47Δ treatment in vivo significantly inhibited tumor growth compared with mock treatment. This study demonstrates that oHSV is effective against breast cancer stem cells and could be a beneficial strategy for treating breast cancer patients.
登录
查看更多内容
影响因子：
82.9
作者：
MINETA, T;RABKIN, SD;MARTUZA, RL
通讯作者：
MARTUZA, RL
影响因子：
3.8
作者：
Li HZ;Yi TB;Wu ZY
通讯作者：
Wu ZY
肝细胞癌相关成纤维细胞通过 PGE2 和 IDO 触发 NK 细胞功能障碍
影响因子：
9.7
作者：
Li, Tuanjie;Yang, Yang;Chen, Guihua
通讯作者：
Chen, Guihua
影响因子：
12.4
作者：
Eriksson, Minna;Guse, Kilian;Hemminki, Akseli
通讯作者：
Hemminki, Akseli
影响因子：
11.2
作者：
Liu, RB;Varghese, S;Rabkin, SD
通讯作者：
Rabkin, SD