文章目录

骨髓NG2+/Nestin+间充质干细胞通过TGF-β2驱动DTC休眠

原文发布日期：2021-03-11

英文摘要：

摘要翻译：

在骨髓微环境中，乳腺癌细胞（BC）中的分散肿瘤细胞（DTCs）可以静止 dormant decades。NG2+/Nestin+间充质干细胞 mesenchymal stem cells 促进血细胞 stem cell quiescence quiescent状态。我们揭示了，在骨髓中periarteriolar的NG2+/Nestin+间充质干细胞 mesenchymal stem cells 同样可以指导 BC 的分散肿瘤细胞进入静止 state。这些NG2+/Nestin+间充质干细胞 mesenchymal stem cells 产生转形生长因子（TGF）-β2和骨转生蛋白（BMP）7，并激活依赖于TGFBRIII和BMPRII的静止途径，通过p38-激酶 kinase途径诱导p27的诱导。基因减少间充质干细胞或使用NG2-CreER导鼠 conditional knockout TGF-β2导致原本处于静止状态 p27+/Ki67−肿瘤细胞向骨转移 outgrowth 增生。此外，无系统性复发的雌激素受体阳性 BC 病人显示在骨髓中更频繁地检测到TGF-β2和BMP7。我们的结果直接证明了血细胞 stem cell quiescence niches 控制 BC 的分散肿瘤细胞 quiescence，并提示影响NG2+/Nestin+间充质干细胞 niche 家庭维持的年龄或外在因素可能引发从静止状态 break out 和 BC 骨转移 relapse。

原文链接：

文章：

骨髓NG2+/Nestin+间充质干细胞通过TGF-β2驱动DTC休眠

Bone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2

原文发布日期：2021-03-11

英文摘要：

In the bone marrow (BM) microenvironment, where breast cancer (BC)-disseminated tumor cells (DTCs) can remain dormant for decades, NG2+/Nestin+ mesenchymal stem cells (MSCs) promote hematopoietic stem cell quiescence. Here we reveal that periarteriolar BM-resident NG2+/Nestin+ MSCs can also instruct BC DTCs to enter dormancy. NG2+/Nestin+ MSCs produce transforming growth factor (TGF)-β2 and bone morphogenetic protein (BMP)7 and activate a quiescence pathway dependent on TGFBRIII and BMPRII, which via p38-kinase, results in p27 induction. Genetic depletion of MSCs or conditional knockout of TGF-β2 in MSCs using an NG2-CreER driver led to bone metastatic outgrowth of otherwise dormant p27+/Ki67− DTCs. Also, patients with estrogen receptor-positive BC without systemic recurrence displayed higher frequency of TGF-β2 and BMP7 detection in the BM. Our results provide direct proof that hematopoietic stem cell dormancy niches control BC DTC dormancy and suggest that aging or extrinsic factors that affect the NG2+/Nestin+ MSC niche homeostasis may result in a break from dormancy and BC bone relapse.