Angiogenesis in vestibular schwannomas: expression of extracellular matrix factors MMP-2, MMP-9, and TIMP-1.
OBJECTIVE
Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are potent mediators of tumor angiogenesis. It has been demonstrated that vestibular schwannoma VEGF expression correlates with tumor growth pattern, whereas knowledge on the expression of MMPs is lacking. This study targets the angiogenic process by investigation of tumor expression of MMP-2, MMP-9, and tissue inhibitors of metalloproteinase (TIMP)-1. A possible correlation with gender, patient age, symptom duration, tumor size, and the absolute and relative growth rate is explored.


METHODS
Prospective vestibular schwannoma tissue sampling for ELISA and immunohistochemical determination of MMP-2, MMP-9 and TIMP-1.


METHODS
Thirty-four patients with a sporadic, noncystic, vestibular schwannoma were selected prospectively. Repeated, preoperative magnetic resonance imaging determined the tumor growth pattern. Following translabyrinthine resection, an enzyme-linked immunosorbent assay was used for determination of the MMP-2, MMP-9, and TIMP-1 concentration in tumor sample homogenates. Immunohistochemical labeling was performed in 12 randomly selected tumors.


RESULTS
: All tumor homogenates expressed measurable MMP-9, MMP-2, and TIMP-1. Immunolabeling localized MMP-9 expression to the tumor cells, whereas MMP-2 and TIMP-1 was found interstitially. A significant correlation existed between the concentration MMP-9 and absolute tumor growth rate, whereas a weak correlation occurred for the relative growth rate.


CONCLUSIONS
Vestibular schwannomas express MMP-2, MMP-9, and TIMP-1 and the tumor concentration of MMP-9 correlates with absolute tumor growth rate, but not with age, gender, symptom duration, or preoperative tumor size. No correlations existed between any clinical parameter and MMP-2 or TIMP-1 expression. We conclude that MMP-9 appears to be involved in the growth of vestibular schwannomas.
Møller
Martin Nue
MN
Department of Otorhinolaryngology, Head and Neck Surgery, Gentofte University Hospital, Hellerup, Denmark.
Werther
Kim
K
Nalla
Amarnadh
A
Stangerup
Sven-Eric
SE
Thomsen
Jens
J
Bøg-Hansen
Thorkild C
TC
Nielsen
Hans Jørgen
HJ
Cayé-Thomasen
Per
P
D000328:Adult; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000201:enzymology* / Q000473:pathology; D009464:Neuroma, Acoustic / Q000098:blood supply* / Q000201:enzymology / Q000601:surgery; D011446:Prospective Studies; D012334:RNA, Neoplasm / Q000235:genetics*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics*
D012334:RNA, Neoplasm; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9