体外共培养人骨髓间充质干细胞与乳腺癌细胞可促进癌细胞的侵袭和迁移能力

Human mesenchymal stem cells promote breast cancer cells migration and invasion by co-culture in vitro

目的探讨人骨髓间充质干细胞(h BM-MSCs)与乳腺癌细胞共培养对癌细胞转移能力的影响。方法 ELISA检测BM-MSCs分泌细胞因子的水平。Transwell小室将BM-MSCs与乳腺癌细胞系MCF-7和MDB-MA-231分别共培养,比较共培养前后乳腺癌细胞的侵袭和迁移能力。Western blot检测p-STAT3和p-ERK等信号通路的激活情况。实时定量RT-PCR检测侵袭转移相关基因MMP-2和MMP-9的表达水平。结果 BM-MSCs分泌大量的细胞因子HGF、IL-6、VEGF和TGF-β1。与BM-MSCs共培养后,乳腺癌细胞MCF-7(P<0.01)和MDB-MA-231(迁移P<0.05,侵袭P<0.01)迁移和侵袭能力显著增加,p-STAT3和p-ERK信号通路激活(P<0.01),侵袭转移相关靶基因MMP-2和MMP-9表达水平上调(P<0.01)。结论 BM-MSCs与乳腺癌细胞共培养可以促进乳腺癌细胞的迁移和侵袭。

Objective To study the effect of human bone marrow derived MSCs （hBM-MSCs） on the migration and invasion capacity of breast cancer cells in a co-culture system. Methods Cytokines secreted by BM-MSCs were detected using ELISA assay. Tumor microenvironment was simulated by co-culturing of BM-MSCs with breast cancer cell lines （ MCF-7 and MDB-MA-231 ） separately. Migration and invasion were compared after co-culture using Transwell system. Activation of signal transducer and activator of transcription 3 （ STAT3 ） was detected by Western blot. Experession of metastasis-associated gene matrix metalloproteinases （MMP-2 and MMP-9） were detected by reahime RT-PCR. Results HGF, IL-6, VEGF and TGF β 1 were detected in the medium of BM-MSCs. Co-culturing with BM-MSCs can significantly enhance the migration and invasion capacity of breast cancer cells （ the migration and invasion of MCF-7 （P 〈 0. 01 ） ; the migration of MDA-231 （P 〈 0. 05 ） ; the invasion of MDA-231 （P 〈0.05 ）. Signaling pathway of p-STAT3 and p-ERK were dramatically ac MMP-2 and MMP-9 increased markedly （P 〈 0.01 ）. Conclusions BM capacity of breast cancer cells by indirect co-culture of the two cell line tivated （P 〈 0. 01 ）, and the expression -MSCs may promote migration and invasion S.