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Angiogenesis in vestibular schwannomas: Expression of extracellular matrix factors MMP-2, MMP-9, and TIMP-1

Authors

  • Martin Nue Møller MD,

    1. Department of Otorhinolaryngology, Head and Neck Surgery, Gentofte University Hospital, Hellerup , University of Copenhagen, Copenhagen
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  • Kim Werther MD, PhD,

    1. ENT Clinic, Roskilde , University of Copenhagen, Copenhagen
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  • Amarnadh Nalla MSc,

    1. Faculty of Health Sciences , University of Copenhagen, Copenhagen
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  • Sven-Eric Stangerup MD,

    1. Department of Otorhinolaryngology, Head and Neck Surgery, Gentofte University Hospital, Hellerup , University of Copenhagen, Copenhagen
    2. Faculty of Health Sciences , University of Copenhagen, Copenhagen
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  • Jens Thomsen MD, DMSc,

    1. Department of Otorhinolaryngology, Head and Neck Surgery, Gentofte University Hospital, Hellerup , University of Copenhagen, Copenhagen
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  • Thorkild C. Bøg-Hansen PhD,

    1. Protein Laboratory, Institute of Molecular Pathology , University of Copenhagen, Copenhagen
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  • Hans Jørgen Nielsen MD, DMSc,

    1. Faculty of Health Sciences , University of Copenhagen, Copenhagen
    2. Department of Surgical Gastroenterology, University Hospital Hvidovre, Hvidovre, Denmark
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  • Per Cayé-Thomasen MD, DMSc

    Corresponding author
    1. Department of Otorhinolaryngology, Head and Neck Surgery, Gentofte University Hospital, Hellerup , University of Copenhagen, Copenhagen
    2. Faculty of Health Sciences , University of Copenhagen, Copenhagen
    • Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Gentofte, DK-2900 Hellerup, Denmark
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  • The authors have no funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis:

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.

Study Design:

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. Laryngoscope, 2010

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