title: Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas.
abstract: BACKGROUND
  Leiomyomas growth involves cellular hypertrophy, modulation of mitotic activity and upregulation of extracellular matrix (ECM). Vascular factors and matrix metalloproteinases (MMPs) play a coordinated role during neoplasia and tissue remodeling. The present study investigates the role of angiogenic factor vascular endothelial growth factor (VEGF)-A with the activity of main gelatinases, MMP-2/MMP-9 and their tissue inhibitor TIMP-1 in patients with leiomyomas.
  
  
  METHODS
  Peripheral blood of 46 women with uterine leiomyomas was obtained prior hysterectomy to assess VEGF-A, MMP-2, -9, TIMP-1 levels by enzyme-linked immunosorbent assay compared to 39 healthy controls. Protein expression levels of VEGF-A, MMP-2 and MMP-9 were evaluated by western immunoblotting and immunohistochemistry in leiomyomas tissue specimens after hysterectomy. Furthermore, the activity of gelatinases in leiomyoma tissue extracts and control myometrium was evaluated by semi-quantitative zymography.
  
  
  RESULTS
  Circulating levels of VEGF-A, MMP-2 and TIMP-1 were significantly elevated in leiomyoma patients compared to controls (p<0.001, p=0.004, p=0.003, respectively). A positive correlation was found between VEGF-A and MMP-2 (p=0.021) as well as MMP-9 (p=0.001) peripheral levels in the patient's group. Furthermore, increased VEGF-A protein levels were detected in leiomyoma tissue compared to control myometrium, followed by increased localization of both VEGF-A and MMP-2 in the ECM embedding bundles of smooth muscle cells of leiomyomas. The activity of MMP-2 was significantly higher in leiomyomas than normal myometrium in all investigated tissues.
  
  
  CONCLUSIONS
  This study demonstrates a possible coordinated role of VEGF-A and MMP-2 during uterine leiomyomas growth and angiogenesis with potential prognostic significance.
authors.forename: Porfyrios
authors.initials: P
authors.lastname: Korompelis
authors.forename: Christina
authors.initials: C
authors.lastname: Piperi
authors.forename: Christos
authors.initials: C
authors.lastname: Adamopoulos
authors.forename: Georgia
authors.initials: G
authors.lastname: Dalagiorgou
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: Athanasia
authors.initials: A
authors.lastname: Sepsa
authors.forename: Aris
authors.initials: A
authors.lastname: Antsaklis
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
mesh_terms: D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007889:Leiomyoma / Q000097:blood / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000097:blood / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism*
chemical_list: C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9