Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue

Mol Med Rep. 2015 Jul;12(1):737-45. doi: 10.3892/mmr.2015.3415. Epub 2015 Mar 4.

Abstract

Vestibular schwannomas, also known as acoustic neuromas, are benign tumors, which originate from myelin-forming Schwann cells. They develop in the vestibular branch of the eighth cranial nerve in the internal auditory canal or cerebellopontine angle. The clinical progression of the condition involves slow and progressive growth, eventually resulting in brainstem compression. The objective of the present study was to investigate the expression level and the localization of the pro-inflammatory cytokines, transforming growth factor-β1 (TGF-β1) interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), as well as the adhesion molecules, intracellular adhesion molecule-1 and vascular endothelial growth factor (VEGF), in order to determine whether these factors are involved in the transformation and development of human vestibular schwannoma. The present study investigated whether changes in inflammation are involved in tumor growth and if so, the mechanisms underlying this process. The results of the current study demonstrated that pro-inflammatory cytokines, including TGF-β1, IL-1β and IL-6 exhibited increased expression in human vestibular schwannoma tissue compared with normal vestibular nerve samples. TNF-α was weakly expressed in Schwann cells, confirming that a lower level of this cytokine is involved in the proliferation of Schwann cells. Neoplastic Schwann cells produce pro-inflammatory cytokines that may act in an autocrine manner, stimulating cellular proliferation. In addition, the increased expression of VEGF in vestibular schwannoma compared with that in normal vestibular nerve tissue, suggests that this factor may induce neoplastic growth via the promotion of angiogenesis. The present findings suggest that inflammation may promote angiogenesis and consequently contribute to tumor progression. In conclusion, the results of the present study indicated that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in vestibular schwannoma. Further studies are necessary to confirm the involvement of these factors in the growth of neoplasms and to develop inhibitors of pro-inflammatory cytokines as a potential treatment option in the future.

MeSH terms

  • Aged
  • Cell Adhesion Molecules / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-1beta / biosynthesis*
  • Interleukin-6 / biosynthesis*
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Neuroma, Acoustic / genetics*
  • Neuroma, Acoustic / pathology
  • Schwann Cells / metabolism
  • Schwann Cells / pathology
  • Transforming Growth Factor beta1 / biosynthesis*
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vestibular Nerve / metabolism
  • Vestibular Nerve / pathology

Substances

  • Cell Adhesion Molecules
  • Interleukin-1beta
  • Interleukin-6
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A