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73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

Expression of key components of the AHR genomic pathway in brain metastases of malignant melanoma

Expression verschiedener Komponenten des genomischen AHR Pathways im malignen Melanom

Meeting Abstract

Suche in Medline nach

  • Isabel Peto-Madew - Universitätsklinikum Köln, Klinik für Neurochirurgie, Köln, Deutschland
  • Roland Goldbrunner - Universitätsklinikum Köln, Klinik für Neurochirurgie, Köln, Deutschland
  • presenting/speaker Marco Timmer - Universitätsklinikum Köln, Klinik für Neurochirurgie, Köln, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocV178

doi: 10.3205/22dgnc172, urn:nbn:de:0183-22dgnc1726

Veröffentlicht: 25. Mai 2022

© 2022 Peto-Madew et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objective: The Aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor initially linked to exogenic carcinogenic agents such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). In 2011, the tryptophan (TRP) catabolite kynurenine (KYN) was identified as the first endogenous ligand activating the AHR pathway. AHR has been shown to be involved in several biochemical pathways and cellular processes such as the cell cycle, cell migration, tumorigenesis, and immune function. AHR is expressed in cells of the central nervous system and dysregulation of AHR, its nuclear translocator (ARNT), its Repressor AHRR and the KYN building Enzyme TRP-2,3-dioxygenase 2 (TDO) has been linked to poor survival in patients with Glioblastoma. In this study we aimed to evaluate a potential role of AHR, ARNT, AHRR and TDO in brain metastases of malignant melanoma.

Methods: Western Blot analysis was used for quantitative analysis of Ahr, Arnt, TDO and AHRR. 16 matched tumors were obtained via neurosurgery, 8 metastatic and 8 recurrent tumors and immediately frozen using liquid nitrogen. The proteins were extracted using RIPA lysis buffer. Western Blot was performed, followed by detection via peroxidase linked secondary antibodies.

Results: Ahr was upregulated in Metastases (0,5854+/-0,2946) and slightly also in the recurrent tumor (0,2569+/-0.1812) compared to control brain tissue (0,0677+/-0,0395). In the case of ARNT, expression was only slightly upregulated in metastases (0,1683+/-0,1075) and in the recurrent tumor (0,1827+/-0,1779) compared to control tissue (0,1138+/-0,0457). AHRR was only upregulated in metastatic tissue (1,2285+/-0,5474), while being slightly downregulated in recurrent tissue (0,3644+/-0,453), comparative to the control group (0,5546+/-0,1299). The expression of TDO was upregulated in both metastatic (0,1282+/-0,0482) and recurrent (0,1291+/-0,0661) tissue versus normal tissue (0,0929+/-0,0678).

Conclusion: All components of the AHR pathway are upregulated in cerebral metastases compared to controls, suggesting a possible target for therapy with AHR inhibitors or other drugs inhibiting the genomic pathway. In the recurrent brain metastases, parts of the pathway are either similar to metastatic tissue, as is the case in the expression of ARNT and TDO, suggesting a persistence of the removed metastatic tissue, or downregulated, suggesting dedifferentiation of the recurrent cancer to the initial metastases.