Ding Honghua, Wang Chungang
Department of Oncology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China.
Department of Radiation Oncology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
Tumour Biol. 2015 Sep;36(9):6759-64. doi: 10.1007/s13277-015-3357-7. Epub 2015 Apr 3.
The molecular regulation of the growth of colorectal cancer (CRC) cells is not completely understood. Here, we report expression of Lgr5, a stem cell marker for the intestine and hair follicle, in some of the CRC cells in the patients. To determine the role of Lgr5-positive cells in the tumorigenesis of CRCs, we prepared an adeno-associated virus (AAV) that carries diphtheria toxin fragment A (DTA) under the control of Lgr5 promoter (AAV-pLgr5-DTA). Transduction of several CRC cell lines with this virus selectively killed Lgr5-positive cells, resulting in significant inhibition of the CRC cell growth in vitro and in vivo. Thus, our data highlight a potential role of Lgr5-positive cells in the tumorigenesis of CRCs, and suggest that treating these Lgr5-positive cells in CRCs may substantially improve the outcome of CRC therapy.
结直肠癌(CRC)细胞生长的分子调控机制尚未完全明确。在此,我们报告了在部分CRC患者的肿瘤细胞中存在Lgr5的表达,Lgr5是一种肠道和毛囊干细胞标志物。为了确定Lgr5阳性细胞在CRC肿瘤发生中的作用,我们制备了一种腺相关病毒(AAV),该病毒携带在Lgr5启动子控制下的白喉毒素片段A(DTA)(AAV-pLgr5-DTA)。用这种病毒转导几种CRC细胞系可选择性杀死Lgr5阳性细胞,从而在体外和体内显著抑制CRC细胞生长。因此,我们的数据突出了Lgr5阳性细胞在CRC肿瘤发生中的潜在作用,并表明针对CRC中这些Lgr5阳性细胞进行治疗可能会显著改善CRC治疗的效果。