title: 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.
abstract: 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 microenvironment 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-κB (NF-κB) signaling pathway may be involved in these effects.
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Weng
authors.affiliation: Center for Laboratory Teaching and Management, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Minghao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Mengtian
authors.initials: M
authors.lastname: Fan
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yangliu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D060833:Cellular Microenvironment / Q000235:genetics*; D018920:Coculture Techniques / Q000379:methods; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics*; D010010:Osteoclasts / Q000382:microbiology; D015398:Signal Transduction / Q000235:genetics
chemical_list: C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D020929:Mitogen-Activated Protein Kinase Kinases