Delivery of Functional Anti-miR-9 by Mesenchymal Stem Cell-derived Exosomes to Glioblastoma Multiforme Cells Conferred Chemosensitivity.
Delivery of Functional Anti-miR-9 by Mesenchymal Stem Cell-derived Exosomes to Glioblastoma Multiforme Cells Conferred Chemosensitivity.
复制标题
DOI：
10.1038/mtna.2013.60
复制
发表时间：
2013-10-01
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
多形性胶质母细胞瘤（GBM）是成人脑中最常见和最致命的肿瘤，通常显示出化疗和放射抗性。微小RNA（miR）调节生理过程，例如GBM细胞对替莫唑胺（TMZ）的抗性。尽管miR是癌症治疗的有吸引力的靶标，但这种方法的有效性需要靶向递送。间充质干细胞（MSC）可以迁移到癌症部位，包括GBM。我们报告了TMZ耐药GBM细胞中miR-9的增加。miR-9参与药物外排转运蛋白P-糖蛋白的表达。为了阻断miR-9，开发了用Cy 5标记的抗miR-9的方法。染料转移研究表明GBM细胞和MSC之间的细胞内通讯。这通过间隙连接细胞间通讯和微泡的释放而发生。在两种情况下，将抗miR-9从MSC转移到GBM细胞。然而，主要的转移形式发生在微泡中。向耐药GBM细胞递送抗miR-9逆转了多药转运蛋白的表达，并使GBM细胞对TMZ敏感，如细胞死亡和半胱天冬酶活性增加所示。数据显示MSC在合成的抗miR-9的功能性递送以逆转GBM细胞的化学抗性中的潜在作用。
Glioblastoma multiforme (GBM), the most common and lethal tumor of the adult brain, generally shows chemo- and radioresistance. MicroRNAs (miRs) regulate physiological processes, such as resistance of GBM cells to temozolomide (TMZ). Although miRs are attractive targets for cancer therapeutics, the effectiveness of this approach requires targeted delivery. Mesenchymal stem cells (MSCs) can migrate to the sites of cancers, including GBM. We report on an increase in miR-9 in TMZ-resistant GBM cells. miR-9 was involved in the expression of the drug efflux transporter, P-glycoprotein. To block miR-9, methods were developed with Cy5-tagged anti-miR-9. Dye-transfer studies indicated intracellular communication between GBM cells and MSCs. This occurred by gap junctional intercellular communication and the release of microvesicles. In both cases, anti-miR-9 was transferred from MSCs to GBM cells. However, the major form of transfer occurred with the microvesicles. The delivery of anti-miR-9 to the resistant GBM cells reversed the expression of the multidrug transporter and sensitized the GBM cells to TMZ, as shown by increased cell death and caspase activity. The data showed a potential role for MSCs in the functional delivery of synthetic anti-miR-9 to reverse the chemoresistance of GBM cells.
登录
查看更多内容
影响因子：
10.8
作者：
Cogolludo A;Moreno L;Frazziano G;Moral-Sanz J;Menendez C;Castañeda J;González C;Villamor E;Perez-Vizcaino F
通讯作者：
Perez-Vizcaino F
影响因子：
3.7
作者：
Pendleton C;Li Q;Chesler DA;Yuan K;Guerrero-Cazares H;Quinones-Hinojosa A
通讯作者：
Quinones-Hinojosa A
影响因子：
11.2
作者：
Lim, Philip K.;Bliss, Sarah A.;Rameshwar, Pranela
通讯作者：
Rameshwar, Pranela
影响因子：
50.5
作者：
Schaich, M.;Kestel, L.;Krex, D.
通讯作者：
Krex, D.
影响因子：
6
作者：
Bao, Lili;Hazari, Sidhartha;Dash, Srikanta
通讯作者：
Dash, Srikanta