ADAM9: A novel player in vestibular schwannoma pathogenesis

Breun, Maria; Schwerdtfeger, Alexandra; Martellotta, Donato Daniel; Keßler, Almuth F.; Monoranu, Camelia; Matthies, Cordula; Löhr, Mario; Hagemann, Carsten

doi:10.3892/ol.2020.11299

Cited by 7 publications

(14 citation statements)

References 33 publications

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“…We were the first to describe ADAM9 overexpression in VS, suggesting it might be a marker for tumor growth and invasiveness [5]. However, our study was descriptive in nature and we only could speculate on ADAM9 regulation and function.…”

Section: Discussionmentioning

confidence: 86%

“…Its proteolytic activity also releases cytokines and growth factors and it modifies the ECM by interacting with integrins [4]. In previous experiments we showed an 8.8 times higher ADAM9 mRNA-expression in VS compared to healthy vestibular nerves and suggested that ADAM9 inhibition may be of significance for VS pathogenesis and potential medical treatment [5]. Furthermore, we discussed whether ADAM9 might interact with the VS cell-matrix [5].…”

Section: Introductionmentioning

confidence: 83%

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Analysis of ADAM9 regulation and function in vestibular schwannoma primary cells

et al. 2020

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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 not regulated by Merlin in VS. However, ADAM9 knock down led to 58% reduction in cell numbers in VS primary cell cultures (p < 0.0001). 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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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 83%

Analysis of ADAM9 regulation and function in vestibular schwannoma primary cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…We were the rst to describe ADAM9 overexpression in VS, suggesting it might be a marker for tumor growth and invasiveness [3]. However, our study was descriptive in nature and we only could speculate on ADAM9 regulation and function.…”

Section: Discussionmentioning

confidence: 88%

“…Recently, we showed that a disintegrin and metalloproteinase 9 (ADAM9) mRNA-expression is 8.8 times higher in VS compared to healthy vestibular nerves and we suggested that ADAM9 inhibition may be of signi cance for VS pathogenesis and potential medical treatment [3]. Furthermore, we discussed whether ADAM9 might interact with the VS cell-matrix [3], since it is known to promote tumor invasion by such interactions [4]. In particular, this enzyme liberates membrane-bound proteins by an enzymatic modi cation called "shedding" and therefore plays a role in tumor growth and invasiveness [4].…”

Section: Introductionmentioning

confidence: 99%

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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“…In addition, PDGFC and PI3K genes were also up-regulated, both of which are involved in cell proliferation and growth [ 86 ]. Members of the metalloproteinase protein (ADAM) family are therapeutic targets in many solid tumors, ADAM9 mRNA expression is 8.8-fold higher in vestibular schwannomas compared with normal tissues, and the expression level of ADAM9 is significantly correlated with hearing loss in patients and may be a marker for judging tumor growth and invasion [ 87 ].…”

Section: Mrna In Peripheral Nervous Tumorsmentioning

confidence: 99%

The role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors

et al. 2021

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Neural tumors can generally be divided into central nervous system tumors and peripheral nervous tumors. Because this type of tumor is located in the nerve, even benign tumors are often difficult to remove by surgery. In addition, the majority of neural tumors are malignant, and it is particular the same for the central nervous system tumors. Even treated with the means such as chemotherapy and radiotherapy, they are also difficult to completely cure. In recent years, an increasingly number of studies have focused on the use of mRNA to treat tumors, representing an emerging gene therapy. The use of mRNA can use the expression of some functional proteins for the treatment of genetic disorders or tissue repair, and it can also be applied to immunotherapy through the expression of antigens, antibodies or receptors. Therefore, although these therapies are not fully-fledged enough, they have a broad research prospect. In addition, there are many ways to treat tumors using mRNA vaccines and exosomes carrying mRNA, which have drawn much attention. In this study, we reviewed the current research on the role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors, and examine the future research prospects of mRNA in neural tumors and the opportunities and challenges that will arise in the future application of clinical treatment.

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ADAM9: A novel player in vestibular schwannoma pathogenesis

Cited by 7 publications

References 33 publications

Analysis of ADAM9 regulation and function in vestibular schwannoma primary cells

Analysis of ADAM9 regulation and function in vestibular schwannoma primary cells

Analysis of ADAM9 Regulation and Function in Vestibular Schwannoma Primary Cells

The role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors

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