Metalloproteinases in juvenile angiofibroma--a collagen rich tumor.
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.
Duerr
Stephan
S
Department of Otorhinolaryngology, Head and Neck Surgery, University of Erlangen-Nuremberg, D-91054 Erlangen, Germany.
Wendler
Olaf
O
Aigner
Thomas
T
Karosi
Stefanie
S
Schick
Bernhard
B
D000293:Adolescent; D000328:Adult; D018322:Angiofibroma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D009669:Nose Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014420:Turbinates / Q000201:enzymology / Q000473:pathology
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D045726:Metalloproteases