Metalloproteinases in juvenile angiofibroma--a collagen rich tumor.

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.

• Authors: Stephan Duerr, Olaf Wendler, Thomas Aigner, Stefanie Karosi, Bernhard Schick
• Journal: Human pathology (Hum Pathol) Vol. 39 Issue 2 Pg. 259-68 (Feb 2008) ISSN: 0046-8177 [Print] United States
• PMID: 17950779 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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