title: Adrenomedullin expression in epithelial ovarian cancers and promotes HO8910 cell migration associated with upregulating integrin α5β1 and phosphorylating FAK and paxillin.
abstract: BACKGROUND
  Epithelial ovarian cancer (EOC) is one of the leading causes of cancer deaths in women worldwide. Adrenomedullin (AM) is a multifunctional peptide which presents in various kinds of tumors.
  
  
  METHODS
  In this study, we characterized the expression and function of AM in epithelial ovarian cancer using immunohistochemistry staining. Exogenous AM and small interfering RNA (siRNA) specific for AM receptor CRLR were treated to EOC cell line HO8910. Wound healing assay and flow cytometry were used to measure the migration ability and expression of integrin α5 of HO8910 cells after above treatments. Western blot was used to examine the phosphorylation of FAK and paxillin.
  
  
  RESULTS
  We found that patients with high AM expression showed a higher incidence of metastasis, larger residual size of tumors after cytoreduction and shorter disease-free and overall survival time. Exogenous AM induced ovarian cancer cell migration in time- and dose- dependent manners. AM upregulated the expression of integrin α5 and phosphorylation of FAK, paxillin as well.
  
  
  CONCLUSIONS
  Our results suggested that AM contributed to the progression of EOC and had additional roles in EOC cell migration by activating the integrin α5β1 signaling pathway. Therefore, we presumed that AM could be a potential molecular therapeutic target for ovarian carcinoma.
authors.affiliation: Department of Gynecology, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Boya
authors.initials: B
authors.lastname: Deng
authors.forename: Siyang
authors.initials: S
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Miao
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Han
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Wen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D053607:Adrenomedullin / Q000235:genetics*; D037282:Calreticulin / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D051419:Paxillin / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D015398:Signal Transduction
chemical_list: D037282:Calreticulin; D039081:Integrin alpha5beta1; D051419:Paxillin; D053607:Adrenomedullin; D051417:Focal Adhesion Kinase 1