BMP9 inhibits the growth and migration of lung adenocarcinoma A549 cells in a bone marrow stromal cell-derived microenvironment through the MAPK/ERK and NF-κB pathways
BMP9 inhibits the growth and migration of lung adenocarcinoma A549 cells in a bone marrow stromal cell-derived microenvironment through the MAPK/ERK and NF-κB pathways
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DOI：
10.3892/or.2016.4796
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发表时间：
2016-07-01
期刊：
影响因子：
4.2
通讯作者：
Shi, Qiong
中科院分区：
文献类型：
--
作者：
Wang, Jing;Weng, Yaguang;Shi, Qiong
骨是肺癌最常见的远处转移部位，特别容易发生溶骨性损害。骨髓来源的细胞和肿瘤细胞分泌的可溶性因子有助于癌细胞的生长和转移，并增强溶骨性损伤。BMP9作为骨形态发生蛋白(BMP)家族中最强大的成骨因子，可以调节多种肿瘤的发展。然而，BMP9在肺癌和骨转移微环境中的作用和潜在机制还知之甚少。在此，我们检测了BMP9对肺腺癌A549细胞增殖和迁移的抑制作用。建立A549细胞与骨髓源性细胞(HS-5)共培养体系后，发现HS-5细胞促进A549细胞的增殖和迁移，A549和HS-5细胞的转移和破骨细胞相关因子IL-6和IL-8水平升高。但BMP9抑制A549细胞在骨微环境中的增殖和迁移，并降低IL-6和IL-8水平。此外，丝裂原活化蛋白激酶(MAPK/ERK)和核因子-kappaB(NF-kappa B)信号通路可能参与了这些作用。
Bone is the most common distant metastatic site of lung cancer, and is particularly prone to osteolytic damage. Soluble factors secreted from bone marrow-derived cells and tumor cells contribute to the growth and metastasis of cancer cells, and enhance osteolytic damage. BMP9, as the most powerful osteogenetic factor of the bone morphogenetic protein (BMP) family, can regulate the development of various tumors. However, the effects and underlying mechanisms of BMP9 in regards to lung cancer and the bone metastatic micro environment are poorly understood. Here, we determined the inhibitory effects of BMP9 on the proliferation and migration of lung adenocarcinoma A549 cells. When a co-culture system of A549 cells and bone marrow-derived cells (HS-5) was established, it was shown that HS-5 cells promoted the proliferation and migration of A549 cells, and metastasis and osteoclast-related factors IL-6 and IL-8 were increased in the A549 and HS-5 cells. However, BMP9 inhibited the proliferation and migration of the A549 cells in the bone microenvironment, and decreased the levels of IL-6 and IL-8. In addition, mitogen-activated protein kinase (MAPK/ERK) and nuclear factor-kappa B (NF-kappa B) signaling pathway may be involved in these effects.