title: BMP9 regulates cross-talk between breast cancer cells and bone marrow-derived mesenchymal stem cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  After establishing a co-culture system composed of MDA-MB-231 breast 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 expression in HS-5 cells and metastases-related genes in MDA-MB-231 cells.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
authors.forename: Shaoheng
authors.initials: S
authors.lastname: Wan
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Liu
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Weng
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Ren
authors.forename: Chang
authors.initials: C
authors.lastname: Fei
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Jinshu
authors.initials: J
authors.lastname: Wang
authors.forename: Yayun
authors.initials: Y
authors.lastname: Jiang
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.forename: Tongchuan
authors.initials: T
authors.lastname: He
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000235:genetics* / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008819:Mice, Nude; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D017077:Culture Media, Conditioned; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D053245:RANK Ligand; D051057:Proto-Oncogene Proteins c-akt