Oncolytic adenoviruses kill breast cancer initiating CD44+CD24-/Low cells
Oncolytic adenoviruses kill breast cancer initiating CD44+CD24-/Low cells
复制标题
DOI：
10.1038/sj.mt.6300300
复制
发表时间：
2007-12-01
影响因子：
12.4
通讯作者：
Hemminki, Akseli
中科院分区：
文献类型：
--
作者：
Eriksson, Minna;Guse, Kilian;Hemminki, Akseli
癌症干细胞已被指示在肿瘤的起始中，并且甚至被发现在已经进行了明显的治愈性疗法之后是复发的原因。在乳腺癌中，它们可能存在于CD 44（+）CD 24（-/低）人群中。使用溶瘤腺病毒提供了一种有吸引力的根除这些细胞的抗肿瘤方法，因为它们通过感染进入，因此它们对通常使干细胞对许多药物具有抗性的那些机制不敏感。我们从患者胸腔积液中分离出CD 44（+）CD 24（-/低）细胞，并证实了干细胞样特征，包括oct 4和sox 2表达和Hoechst 33342排除。CD 44（+）CD 24（-/低）细胞，包括Hoechst排除亚群，可以被溶瘤腺病毒Ad 5/3-Delta 24和Ad5.pk7-Delta 24有效杀死。在小鼠中，CD 44（+）CD 24（-/低）细胞形成原位乳腺肿瘤，但病毒感染阻止肿瘤形成。Ad 5/3-Delta 24和Ad5.pk7-Delta 24对晚期原位CD 44（+）CD 24（-/低）来源的肿瘤有效。综上所述，Ad 5/3-Delta 24和Ad5.pk7-Delta 24可以杀伤CD 44（+）CD 24（-/低），也可以杀伤定向乳腺癌细胞，使其成为治疗乳腺癌的有希望的药物。
Cancer stem cells have been indicated in the initiation of tumors and are even found to be responsible for relapses after apparently curative therapies have been undertaken. In breast cancer, they may reside in the CD44(+)CD24(-/low) population. The use of oncolytic adenoviruses presents an attractive anti-tumor approach for eradication of these cells because their entry occurs through infection and they are, therefore, not susceptible to those mechanisms that commonly render stem cells resistant to many drugs. We isolated CD44(+)CD24(-/low) cells from patient pleural effusions and confirmed stem cell-like features including oct4 and sox2 expression and Hoechst 33342 exclusion. CD44(+)CD24(-/low) cells, including the Hoechst excluding subpopulation, could be effectively killed by oncolytic adenoviruses Ad5/3-Delta 24 and Ad5.pk7-Delta 24. In mice, CD44(+)CD24(-/low) cells formed orthotopic breast tumors but virus infection prevented tumor formation. Ad5/3-Delta 24 and Ad5.pk7-Delta 24 were effective against advanced orthotopic CD44(+)CD24(-/low)-derived tumors. In summary, Ad5/3-Delta 24 and Ad5.pk7-Delta 24 can kill CD44(+)CD24(-/low), and also committed breast cancer cells, making them promising agents for treatment of breast cancer.