Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics.
Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics.
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DOI：
10.1186/bcr1855
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Varticovski L
中科院分区：
文献类型：
--
作者：
Wright MH;Calcagno AM;Salcido CD;Carlson MD;Ambudkar SV;Varticovski L
癌症干细胞是否出现在BRCA 1相关的乳腺癌中并有助于治疗反应尚不清楚。我们从5种不同的Brca 1缺陷小鼠乳腺肿瘤中产生了16种细胞系，并对其癌症干细胞特征进行了表征。来自一个肿瘤的所有细胞系包括增加数量的CD 44 +/CD 24-细胞，其先前被鉴定为人乳腺癌干细胞。来自另一种乳腺肿瘤的所有细胞系均表现出低水平的CD 44 +/CD 24-细胞，但它们含有2%至5.9%的CD 133+细胞，这些细胞以前与其他人类和小鼠肿瘤中的癌症干细胞相关。当在不存在附着而不进行预分选的情况下铺板时，仅富集任一干细胞标志物的那些细胞系形成球状体，其进一步富集表达相应癌症干细胞标志物的细胞。相比之下，当在单层中培养时，针对CD 44 +/CD 24-或CD 133+标记物分选的细胞失去其干细胞表型。在非肥胖糖尿病/严重联合免疫缺陷小鼠中，只有50至100个CD 44 +/CD 24-或CD 133+分选细胞迅速形成肿瘤，而需要50倍至100倍的亲代或干细胞耗竭细胞才能形成少量缓慢生长的肿瘤。在CD 44 +/CD 24-和CD 133+细胞中，干细胞相关基因（包括Oct 4、Notch 1、Aldh 1、Fgfr 1和Sox 1）的表达增加。此外，与亲本或干细胞耗尽的群体相比，针对癌症干细胞标记物和球状体形成细胞分选的细胞对DNA损伤药物的抗性显著更高，并且它们对热休克蛋白-90抑制剂17-DMAG（17-二甲氨基乙氨基-17-去甲氧基格尔德霉素盐酸盐）的药物敏感。Brca 1缺陷小鼠乳腺肿瘤含有异质性癌症干细胞群，CD 44 +/CD 24-细胞代表与人类乳腺癌干细胞相关的群体。
Whether cancer stem cells occur in BRCA1-associated breast cancer and contribute to therapeutic response is not known. We generated and characterized 16 cell lines from five distinct Brca1deficient mouse mammary tumors with respect to their cancer stem cell characteristics. All cell lines derived from one tumor included increased numbers of CD44+/CD24- cells, which were previously identified as human breast cancer stem cells. All cell lines derived from another mammary tumor exhibited low levels of CD44+/CD24- cells, but they harbored 2% to 5.9% CD133+ cells, which were previously associated with cancer stem cells in other human and murine tumors. When plated in the absence of attachment without presorting, only those cell lines that were enriched in either stem cell marker formed spheroids, which were further enriched in cells expressing the respective cancer stem cell marker. In contrast, cells sorted for CD44+/CD24- or CD133+ markers lost their stem cell phenotype when cultured in monolayers. As few as 50 to 100 CD44+/CD24- or CD133+ sorted cells rapidly formed tumors in nonobese diabetic/severe combined immunodeficient mice, whereas 50-fold to 100-fold higher numbers of parental or stem cell depleted cells were required to form few, slow-growing tumors. Expression of stem cell associated genes, including Oct4, Notch1, Aldh1, Fgfr1, and Sox1, was increased in CD44+/CD24- and CD133+ cells. In addition, cells sorted for cancer stem cell markers and spheroid-forming cells were significantly more resistant to DNA-damaging drugs than were parental or stem cell depleted populations, and they were sensitized to the drugs by the heat shock protein-90 inhibitor 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride). Brca1-deficient mouse mammary tumors harbor heterogeneous cancer stem cell populations, and CD44+/CD24- cells represent a population that correlates with human breast cancer stem cells.
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影响因子：
11.5
作者：
Evangelista, Marie;Tian, Hua;de Sauvage, Frederic J.
通讯作者：
de Sauvage, Frederic J.
影响因子：
--
作者：
Calcagno AM;Chewning KJ;Wu CP;Ambudkar SV
通讯作者：
Ambudkar SV
影响因子：
56.9
作者：
FUTREAL, PA;LIU, QY;WISEMAN, R
通讯作者：
WISEMAN, R
影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
影响因子：
11.2
作者：
Dote, Hideaki;Burgan, William E.;Tofilon, Philip J.
通讯作者：
Tofilon, Philip J.