BMP9 regulates cross-talk between breast cancer cells and bone marrow-derived mesenchymal stem cells
BMP9 regulates cross-talk between breast cancer cells and bone marrow-derived mesenchymal stem cells
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DOI：
10.1007/s13402-014-0197-1
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发表时间：
2014-10-01
影响因子：
6.6
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
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作者：
Wan, Shaoheng;Liu, Yuehong;Zhang, Yan
乳腺癌细胞经常转移到远处器官，包括骨骼。已知乳腺癌细胞与骨微环境之间的相互作用会增强肿瘤生长和溶骨性损伤。在这里，我们调查了BMP 9是否在建立由MDA-MB-231乳腺癌细胞和HS-5骨髓间充质干细胞组成的共培养体系并将该体系暴露于BMP 9条件培养基后，我们观察了MDA-MB-231细胞迁移和侵袭能力的变化，以及HS-5细胞中成骨标志物表达和MDA-MB-231细胞中骨转移酶相关基因的变化，发现BMP 9可以抑制MDA-MB-231细胞的迁移和侵袭，促进HS-5细胞的成骨和增殖，在共培养系统中。我们还发现，BMP 9诱导的MDA-MB-231细胞迁移和侵袭的抑制可能是由于HS-5细胞分泌RANK配体（RANKL）减少，导致AKT信号通路阻断所致。从我们的数据我们得出结论，BMP 9抑制乳腺癌细胞的迁移和侵袭，并通过RANK/RANKL信号传导轴调节这两种类型细胞之间的串扰，促进骨髓源性间充质干细胞的成骨分化和增殖。
Breast cancer cells frequently metastasize to distant organs, including bone. Interactions between breast cancer cells and the bone microenvironment are known to enhance tumor growth and osteolytic damage. Here we investigated whether BMP9 (a secretary protein) may change the bone microenvironment and, by doing so, regulate the cross-talk between breast cancer cells and bone marrow-derived mesenchymal stem cells.After establishing a co-culture system composed of MDA-MB-231breast cancer cells and HS-5 bone marrow-derived mesenchymal stem cells, and exposure of this system to BMP9 conditioned media, we assessed putative changes in migration and invasion capacities of MDA-MB-231 cells and concomitant changes in osteogenic marker expressionin HS-5 cells and metastases-related genes in MDA-MB-231 cells.We found that BMP9 can inhibit the migration and invasion of MDA-MB-231 cells, and promote osteogenesis and proliferation of HS-5 cells, in the co-culture system. We also found that the BMP9-induced inhibition of migration and invasion of MDA-MB-231 cells may be caused by a decreased RANK ligand (RANKL) secretion by HS-5 cells, leading to a block in the AKT signaling pathway.From our data we conclude that BMP9 inhibits the migration and invasion of breast cancer cells, and promotes the osteoblastic differentiation and proliferation of bone marrow-derived mesenchymal stem cells by regulating cross-talk between these two types of cells through the RANK/RANKL signaling axis.