Gap Junction-Mediated Import of MicroRNA from Bone Marrow Stromal Cells Can Elicit Cell Cycle Quiescence in Breast Cancer Cells
Gap Junction-Mediated Import of MicroRNA from Bone Marrow Stromal Cells Can Elicit Cell Cycle Quiescence in Breast Cancer Cells
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DOI：
10.1158/0008-5472.can-10-2372
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发表时间：
2011-03-01
期刊：
影响因子：
11.2
通讯作者：
Rameshwar, Pranela
中科院分区：
文献类型：
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作者：
Lim, Philip K.;Bliss, Sarah A.;Rameshwar, Pranela
乳腺癌（BC）的骨髓（BM）转移甚至可以在初次诊断和治疗后数十年复发，这意味着播散的癌细胞在休眠状态下长期存活。在这里，我们研究了微小RNA（miRNA）通过间隙连接和外泌体从BM基质传递到BC细胞在肿瘤细胞静止中的作用。当与BM基质共培养时，MDA-MB-231和T47 D BC细胞停滞在细胞周期的G（0）期。对miRNA表达谱的分析鉴定了许多涉及细胞增殖的miRNA，包括靶向CXCL 12的miR-127、-197、-222和-223。随后，我们发现这些CXCL 12特异性miRNA通过间隙连接从BM基质转运到BC细胞，导致CXCL 12水平降低和增殖减少。含有miRNAs的基质来源的外来体也有助于BC细胞静止，尽管程度低于通过间隙连接传递的miRNAs。这项研究表明，从BM间质转移到BC细胞的miRNA可能在BM转移的休眠中发挥作用。Cancer Res; 71（5）; 1550-60.（C）2011年《非洲标准化评论》。
Bone marrow (BM) metastasis of breast cancer (BC) can recur even decades after initial diagnosis and treatment, implying the long-term survival of disseminated cancer cells in a dormant state. Here we investigated the role of microRNAs (miRNA) transmitted from BM stroma to BC cells via gap junctions and exosomes in tumor cell quiescence. MDA-MB-231 and T47D BC cells arrest in G(0) phase of the cell cycle when cocultured with BM stroma. Analyses of miRNA expression profiles identified numerous miRNAs implicated in cell proliferation including miR-127, -197, -222, and -223 targeting CXCL12. Subsequently, we showed that these CXCL12-specific miRNAs are transported from BM stroma to BC cells via gap junctions, leading to reduced CXCL12 levels and decreased proliferation. Stroma-derived exosomes containing miRNAs also contributed to BC cell quiescence, although to a lesser degree than miRNAs transmitted via gap junctions. This study shows that the transfer of miRNAs from BM stroma to BC cells might play a role in the dormancy of BM metastases. Cancer Res; 71(5); 1550-60. (C)2011 AACR.