CXCR4: A new player in vestibular schwannoma pathogenesis

Breun, Maria; Schwerdtfeger, Alexandra; Martellotta, Donato Daniel; Keßler, Almuth F.; Pérez, José María Hernández; Monoranu, Camelia; Ernestus, Ralf‐Ingo; Matthies, Cordula; Löhr, Mario; Hagemann, Carsten

doi:10.18632/oncotarget.24119

Cited by 36 publications

(40 citation statements)

References 34 publications

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“…This is the first report of in vivo imaging of CXCR4 expression in humans with VS. A recent report from our group evaluating samples of these tumors had demonstrated higher chemokine receptor expression in VS as compared to healthy vestibular nerves, with higher CXCR4 expression levels trending to correlate with greater functional impairment (16). In concordance with in vitro data, receptor expression on the cell surface was visualized by [ 68 Ga]-Pentixafor PET/CT in our cohort in all cases, even in VS as small as 8 mm.…”

Section: Discussionmentioning

confidence: 93%

“…CXCR4 overexpression has been described in more than 30 different tumor entities including breast, prostate, lung, and colon cancer, as well as in neuroblastoma and peripheral nerve sheath tumors (10, 14). Significant overexpression of CXCR4 in both sporadic as well as neurofibromatosis-associated VS was recently demonstrated (15, 16). Therefore, CXCR4 could serve as a new target for systemic therapy with specific inhibitors (e.g., AMD3100) (17, 18).…”

Section: Introductionmentioning

confidence: 99%

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[68Ga]-Pentixafor PET/CT for CXCR4-Mediated Imaging of Vestibular Schwannomas

et al. 2019

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We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [ 68 Ga]Pentixafor. Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [ 68 Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients. Results: [ 68 Ga]Pentixafor PET/CT was visually positive in all cases. SUV mean and SUV max were 3.0 ± 0.3 and 3.8 ± 0.4 and TBR mean and TBR max were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors. Conclusion: Non-invasive imaging of CXCR4 expression using [ 68 Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

[68Ga]-Pentixafor PET/CT for CXCR4-Mediated Imaging of Vestibular Schwannomas

et al. 2019

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“…The extracted protein was measured with the Qubit 2.0 Fluorometer (Thermo Fisher Scienti c, Waltham, MA, USA). Polyacrylamid gel electrophoresis (PAGE) was performed as described [6] and the gel blotted for 7 min using the iBlot system (Thermo Fisher Scienti c, Waltham, MA, USA) set to program 3. The membrane was blocked in TBST (Sigma, Munich, Germany) containing 5% non-fat milk powder (Roth, Karlsruhe, Germany) and probed with antibodies as described previously [6].…”

Section: Western-blotmentioning

confidence: 99%

“…Polyacrylamid gel electrophoresis (PAGE) was performed as described [6] and the gel blotted for 7 min using the iBlot system (Thermo Fisher Scienti c, Waltham, MA, USA) set to program 3. The membrane was blocked in TBST (Sigma, Munich, Germany) containing 5% non-fat milk powder (Roth, Karlsruhe, Germany) and probed with antibodies as described previously [6]. Antibodies NF2 B-12 sc-55575 (Santa Cruz Biotechnology, Dallas, TX, USA), ADAM9 ab186833 (Abcam, Cambridge, UK), and anti--tubulin T6557 (Sigma, Munich, Germany) were utilized diluted in TBST at 1:200, 1:1500, and 1:5000, respectively.…”

Section: Western-blotmentioning

confidence: 99%

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Analysis of ADAM9 Regulation and Function in Vestibular Schwannoma Primary Cells

Nattmann

Breun

Monoranu

et al. 2020

Preprint

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Objective: Recently, we described a disintegrin and metalloproteinase 9 (ADAM9) overexpression by Schwann cells of vestibular schwannoma (VS) and suggested that it might be a marker for VS tumor growth and invasiveness. This research note provides additional data utilizing a small cohort of VS primary cultures and tissue samples. We examined whether reconstitution of Merlin expression in VS cells regulates ADAM9 protein expression and performed lentiviral ADAM9 knock down to investigate possible effects on VS cells numbers. Moreover, the co-localization of ADAM9 and Integrins α6 and α2β1, respectively, was examined by immunofluorescence double staining.Results: ADAM9 expression was confirmed in VS but not regulated by Merlin. However, ADAM9 knock down led to significant 2.38 fold reduced cell numbers in VS primary cell cultures (p<0.001). While ADAM9 and Integrin α2β1 were co-localized in only 22% (2 of 9) of VS, ADAM9 and Integrin α6 were co-localized in 91% (10 of 11) of VS. Therefore, we provide first observations on possible regulatory functions of ADAM9 expression in VS.

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Identification of Predictive Proteins and Biological Pathways for the Tumorigenicity of Vestibular Schwannoma by Proteomic Profiling

Zhang

Shi

et al. 2019

Proteomics Clinical Apps

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Purpose Vestibular schwannomas (VSs) are benign tumors that account for 8–10% of all intracranial tumors. So far, the tumorigenesis of VS has not been fully elucidated. This study is designed to identify differently expressed proteins involved in VS tumorigenesis. Experimental Design An isobaric tag is used for relative and absolute quantification (iTRAQ) approach to characterize the protein expression profiles from pooled VS tissues (n = 12) and pooled matched normal vestibular tissues (n = 12). Results A total of 933 differentially expressed proteins are identified between VS and the matched normal vestibular tissues, with 489 being upregulated and 444 being downregulated. Bioinformatics analyses are performed according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Several of the differentially expressed proteins are validated by western blotting analyses, and upregulation of LGALS1, ANXA1, GRB2, and STAT1 is validated in VS tissue by immunohistochemistry. Conclusions and Clinical Relevance The study represents the successful application of iTRAQ technology to an investigation of VS. Many of the differentially expressed proteins identified here have not been linked to VS before, and these dysregulated proteins may provide potential biomarkers for human VS diagnosis.

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CXCR4: A new player in vestibular schwannoma pathogenesis

Cited by 36 publications

References 34 publications

[68Ga]-Pentixafor PET/CT for CXCR4-Mediated Imaging of Vestibular Schwannomas

[68Ga]-Pentixafor PET/CT for CXCR4-Mediated Imaging of Vestibular Schwannomas

Analysis of ADAM9 Regulation and Function in Vestibular Schwannoma Primary Cells

Identification of Predictive Proteins and Biological Pathways for the Tumorigenicity of Vestibular Schwannoma by Proteomic Profiling

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