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Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas

  • Porfyrios Korompelis , Christina Piperi EMAIL logo , Christos Adamopoulos , Georgia Dalagiorgou , Penelope Korkolopoulou , Athanasia Sepsa , Aris Antsaklis and Athanasios G. Papavassiliou
Published/Copyright: December 3, 2014
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 53 Issue 9

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.

Keywords: matrix metalloproteinase (MMP)-2; MMP-9; TIMP-1; uterine leiomyomas; vascular endothelial growth factor (VEGF)-A
Corresponding author: Christina Piperi, Department of Biological Chemistry, University of Athens Medical School, 75 M. Asias Street, 11527 Athens, Greece, Phone: +30 210 7462610, Fax: +30 210 7791207, E-mail:
aChristina Piperi and Christos Adamopoulos contributed equally to this work.

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Received: 2014-8-5
Accepted: 2014-10-27
Published Online: 2014-12-3
Published in Print: 2015-8-1

©2015 by De Gruyter

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https://doi.org/10.1515/cclm-2014-0798
Keywords for this article
matrix metalloproteinase (MMP)-2; MMP-9; TIMP-1; uterine leiomyomas; vascular endothelial growth factor (VEGF)-A

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. New trends in the long and puzzling history of HbA1c
  4. Review
  5. Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges
  6. Opinion Paper
  7. Possible role of fructosamine 3-kinase genotyping for the management of diabetic patients
  8. EFLM Original Article
  9. Compliance of blood sampling procedures with the CLSI H3-A6 guidelines: An observational study by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PRE)
  10. Genetics and Molecular Diagnostics
  11. Quantitative-fluorescent-PCR versus full karyotyping in prenatal diagnosis of common chromosome aneuploidies in southern Spain
  12. HIF1A and MIF as potential predictive mRNA biomarkers of pre-eclampsia: a longitudinal prospective study in high risk population
  13. General Clinical Chemistry and Laboratory Medicine
  14. Evidence of Crohn’s disease-related anti-glycoprotein 2 antibodies in patients with celiac disease
  15. Myocardial interleukin-6 in the setting of left ventricular mechanical assistance: relation with outcome and C-reactive protein
  16. Different methods to estimate serum free cortisol: a comparison during cortisol tetracosactide testing
  17. Automated immunoassays for the autoantibodies to carbamylated or citrullinated telopeptides of type I and II collagens
  18. Relevance of correction for drift and day-to-day variation in cystatin C measurement: a post-hoc analysis of the PREVEND cohort, with independent replication in the ESTHER cohort
  19. Laboratory utilization improvement through a computer-aided algorithm developed with general practitioners
  20. Quantitation of 1α,25-dihydroxyvitamin D by LC-MS/MS using solid-phase extraction and fixed-charge derivitization in comparison to immunoextraction
  21. Reference Values and Biological Variations
  22. Establishment of trimester-specific thyroid stimulating hormone and free thyroxine reference interval in pregnant Chinese women using the Beckman Coulter UniCel™ DxI 600
  23. Cancer Diagnostics
  24. Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas
  25. Influence of ABO type on global coagulation assay results: effect of coagulation factor VIII
  26. Diabetes
  27. Benchmarking by HbA1c in a national diabetes quality register – does measurement bias matter?
  28. Comparing HbA1c, fasting and 2-h plasma glucose for screening for abnormal glucose regulation in patients undergoing coronary angiography
  29. Erroneous HbA1c measurements in the presence of β-thalassemia and common Chinese hemoglobin variants
  30. Using the likelihood ratio to evaluate allowable total error – an example with glycated hemoglobin (HbA1c)
  31. Two novel haemoglobin variants that affect haemoglobin A1c measurement by ion-exchange chromatography
  32. Analytical performances of the D-100TM hemoglobin testing system (Bio-Rad) for HbA1c assay
  33. Letters to the Editors
  34. Glycation rate of haemoglobins S, C, D, E, J and G, and analytical interference on the measurement of HbA1c with affinity chromatography and capillary electrophoresis
  35. Hemoglobin Valme HBB:c.124T>G: a new hemoglobin variant with diminished oxygen affinity causes interference in hemoglobin A1c measurement in an automated ion-exchange HPLC method
  36. Hemoglobin A1c reported in units and diagnostic cut-offs in relation to the international recommendations
  37. Hemoglobin measurements in samples containing hemoglobin-based oxygen carriers
  38. Serologic false-positive reactions for syphilis in children of allergic purpura
  39. Exploration of the pre-analytical stability of β-lactam antibiotics in plasma and blood – implications for therapeutic drug monitoring and pharmacokinetic studies
  40. Fungal contamination of hyaluronidase solution mimicking fungal joint infection: a preanalytical pitfall in synovial fluid analysis
  41. Stroke and inherited thrombophilia in a Tunisian girl with sickle cell anemia
  42. Faecal haemoglobin concentrations do vary across geography as well as with age and sex: ramifications for colorectal cancer screening
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