title: BMP7 expression in esophageal squamous cell carcinoma and its potential role in modulating metastasis.
abstract: BACKGROUND
  Our previous study showed that BMP7 revealed significantly higher levels in esophageal squamous cell carcinoma (ESCC) tissues with lymph node metastasis compared with non-lymph node metastasis, using gene expression profiling assays. The roles of BMP7 in ESCC is not fully understood.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effect of BMP7 on lymph node metastasis of ESCC and to explore its potential mechanism.
  
  
  METHODS
  Expression of BMP7 in ESCC tissues was evaluated by immunohistochemistry. BMP7 were down-regulated by RNA interference. The protein and mRNA levels of BMP7 were detected by western blot and RT-PCR, respectively. High content screening and transwell assay were used to identify the metastatic ability of tumor cells.
  
  
  RESULTS
  Positivity of BMP7 staining was 57.5 % in the tissues of primary carcinoma with lymph node metastasis compared to tissues without lymph node metastasis, and expression of BMP7 was significantly higher in the cell lines with highly metastatic capacity than that in the cell lines without metastatic ability. Suppression of endogenous BMP7 expression by siRNA in the highly metastatic cell lines resulted in significant reduction in ability of cell migration and invasion in both in vitro and in vivo studies. In addition, inhibition of BMP7 by siRNA also leads to up-regulation of E-cadherin and down-regulation of MMP-9 in the highly metastatic cell lines.
  
  
  CONCLUSIONS
  These findings indicate that BMP7 modulates the expression of E-cadherin and MMP-9, and by which mechanism it may regulate cell migration and metastasis of ESCCs.
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 15 Changle Western Road, Xi'an 710032, People's Republic of China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Xu
authors.forename: Shanhong
authors.initials: S
authors.lastname: Tang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yang
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Jianqin
authors.initials: J
authors.lastname: Kang
authors.forename: Guohong
authors.initials: G
authors.lastname: Zhao
authors.forename: Fan
authors.initials: F
authors.lastname: Feng
authors.forename: Xuewen
authors.initials: X
authors.lastname: Yang
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Liu
authors.initials: L
authors.lastname: Hong
authors.forename: Taiqian
authors.initials: T
authors.lastname: Gong
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: C525819:BMP7 protein, human; D014408:Biomarkers, Tumor; D055419:Bone Morphogenetic Protein 7; D015820:Cadherins; D034741:RNA, Small Interfering; D020780:Matrix Metalloproteinase 9