Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks.
Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks.
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DOI：
10.1158/0008-5472.can-10-0538
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发表时间：
2011-01-15
期刊：
影响因子：
11.2
通讯作者：
Wicha MS
中科院分区：
文献类型：
--
作者：
Liu S;Ginestier C;Ou SJ;Clouthier SG;Patel SH;Monville F;Korkaya H;Heath A;Dutcher J;Kleer CG;Jung Y;Dontu G;Taichman R;Wicha MS
我们利用体外和小鼠异种移植模型来检查乳腺癌干细胞（CSC）和骨髓来源的间充质干细胞（MSC）之间的相互作用。我们证明这两种细胞群都以细胞层次结构组织，其中表达原始乙醛脱氢酶 (ALDH) 的间充质细胞通过涉及 IL6 和 CXCL7 的细胞因子环调节乳腺 CSC。在 NOD/SCID 小鼠中，标记的 MSC 被引入胫骨运输中，到达正在生长的乳腺肿瘤异种移植物的部位，在那里它们通过增加乳腺癌干细胞群来加速肿瘤生长。利用免疫化学，我们在这些肿瘤异种移植物以及原发性人类乳腺癌的冰冻切片中鉴定出了“MSC-CSC 生态位”。骨髓来源的间充质干细胞可以通过产生调节癌症干细胞群的细胞因子网络来加速人类乳腺肿瘤的生长。
We have utilized in vitro and mouse xenograft models to examine the interaction between breast cancer stem cells (CSCs) and bone marrow derived mesenchymal stem cells (MSCs). We demonstrate that both of these cell populations are organized in a cellular hierarchy in which primitive aldehyde dehydrogenase (ALDH) expressing mesenchymal cells regulate breast CSCs through cytokine loops involving IL6 and CXCL7. In NOD/SCID mice, labeled MSCs introduced into the tibia traffic to sites of growing breast tumor xenografts where they accelerate tumor growth by increasing the breast cancer stem cell population. Utilizing immunochemistry, we identified “MSC-CSC niches” in these tumor xenografts as well as in frozen sections from primary human breast cancers. Bone marrow derived mesenchymal stem cell may accelerate human breast tumor growth by generating cytokine networks that regulate the cancer stem cell population.