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

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.

Arthrogenic human synovial cysts: immunohistochemical profile of interleukin-1beta, interleukin-6, tumour necrosis factor-alpha

“…This cytokine is directly involved in the activation of the initial inflammatory process which subsequently leads to fibrosis. The pro-inflammatory cytokine IL-6 plays an important role in the regulation of inflammation and acts in association with TGF-β1, thus leading to an increased profibrotic response [14,15]. IL-6 acts by enhancing the TGF-β1 signal by increasing endocytosis mediated by non-lipid endosomes.…”

Therapy of Sporadic and NF2-Related Vestibular Schwannoma

“…The molecular alterations of VS include NF2 gene mutation/loss/mitotic recombination [5][6][7], abnormal gene expression [8], involvement of immunological factors [9,10], deoxyribonucleic acid (DNA) methylation [11,12] and change in growth factors [13][14][15].…”

Innate and Adaptive Immunity Linked to Recognition of Antigens Shared by Neural Crest-Derived Tumors

“…Because the relevant clinic impact and the difficulties in therapeutic approach the majority of studies is dedicated to vestibular SC. Moreover, in human vestibular SC, immunohistochemical examination reveals an increasing of pro-inflammatory cytokines, including TGF-β1, IL-1β, and IL-6 that may promote growth of the neoplasm [85] supported by the loss of Merlin protein with resulting enhance of NFKB transcriptome [29]. Macrophage colony-stimulating factor (MCS-F) and IL-34 are also associated with growth of vestibular schwannoma, probably by activation of TAMS [86].…”