Metalloproteinases in juvenile angiofibroma--a collagen rich tumor

Hum Pathol. 2008 Feb;39(2):259-68. doi: 10.1016/j.humpath.2007.06.015. Epub 2007 Oct 24.

Abstract

Matrix metalloproteinases (MMPs) act in diverse physiological and pathological conditions such as tumor growth and angiogenesis by cleaving extracellular matrix and nonmatrix substrates. MMPs with gelatinase/collagenase activity have not yet been studied in juvenile angiofibroma, a unique fibrovascular tumor with prominent collagen expression. Quantitative real-time polymerase chain reaction studies, Western blot analysis, immunofluorescence studies, gel zymography, and in situ zymography were used to analyze MMP-1, MMP-2, MMP-9, MMP-13, MMP-14, TIMP-1, and TIMP-2 in 9 juvenile angiofibromas and 2 inferior nasal turbinate specimens. Quantitative real-time polymerase chain reaction found significantly elevated expression of MMP-2, MMP-9, and MMP-14 (P < .05) in tumor tissue compared with the inferior nasal turbinate specimens. Western blot analysis detected more prominent MMP-1, MMP-2, and MMP-9 protein levels in juvenile angiofibromas compared with inferior nasal turbinates, but not MMP-13, MMP-14, TIMP-1, and TIMP-2. Immunofluorescent staining proved a mainly stromal localization of the analyzed MMPs. Only MMP-9 and MMP-14 were also detected in vessel walls. MMP-1, MMP-2, and MMP-13 also stained mast cells. Gel zymography indicated increased MMP-2 and MMP-9 gelatinase activity in juvenile angiofibromas compared with inferior nasal turbinates. Finally, in situ zymography detected very high stromal gelatinase/collagenase activity. This study indicates significant expression of MMPs with gelatinase/collagenase activity in juvenile angiofibromas with evidence of a disturbed balance of MMPs to TIMPs toward enhanced MMP activity. These MMPs are assumed to be involved in tumor pathology with an influence on tumor growth and angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Angiofibroma / enzymology*
  • Angiofibroma / genetics
  • Angiofibroma / pathology
  • Biomarkers, Tumor / metabolism*
  • Collagen / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Male
  • Metalloproteases / genetics
  • Metalloproteases / metabolism*
  • Nose Neoplasms / enzymology*
  • Nose Neoplasms / genetics
  • Nose Neoplasms / pathology
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / analysis
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Turbinates / enzymology
  • Turbinates / pathology

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • RNA, Neoplasm
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Collagen
  • Metalloproteases