
==== Front
Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.080
vdae090.080
Final Category: Novel Targets in CNS Metastases (Non-Immunologic)
AcademicSubjects/MED00300
AcademicSubjects/MED00310
NVTG-06 MELANOMA BRAIN METASTASES BENEFIT FROM HIGH PRKCZ LEVELS
Schöne Lisa Department of Dermatology, Faculty of Medicine and University Hospital, TU Dresden, Dresden, Germany
National Center for Tumor Diseases (NCT/UCC): German Cancer Research Center (DKFZ), Heidelberg, Germany; Medizinische Fakultät and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden – Rossendorf (HZDR), Dresden, Germany, Dresden, Germany

Meinhardt Matthias Institute of Pathology, University Hospital, Dresden, Germany

Mehnert Marie-Christin Department of Dermatology, Faculty of Medicine and University Hospital, TU Dresden, Dresden, Germany
National Center for Tumor Diseases (NCT/UCC): German Cancer Research Center (DKFZ), Heidelberg, Germany; Medizinische Fakultät and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden – Rossendorf (HZDR), Dresden, Germany, Dresden, Germany

Beissert Stefan Department of Dermatology, Faculty of Medicine and University Hospital, TU Dresden, Dresden, Germany
National Center for Tumor Diseases (NCT/UCC): German Cancer Research Center (DKFZ), Heidelberg, Germany; Medizinische Fakultät and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden – Rossendorf (HZDR), Dresden, Germany, Dresden, Germany

Meier Friedegund Department of Dermatology, Faculty of Medicine and University Hospital, TU Dresden, Dresden, Germany
Skin Cancer Center at the University Cancer Center and National Center for Tumor Diseases, Dresden, Germany

Westphal Dana Department of Dermatology, Faculty of Medicine and University Hospital, TU Dresden, Dresden, Germany
National Center for Tumor Diseases (NCT/UCC): German Cancer Research Center (DKFZ), Heidelberg, Germany; Medizinische Fakultät and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden – Rossendorf (HZDR), Dresden, Germany, Dresden, Germany

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i24i25
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

Despite current therapies being proven effective against metastasized melanoma, durable responses against melanoma brain metastases remain pending. The main reasons are brain-specific resistance mechanisms, which motivate investigations into the underlying differences between intracranial and extracranial metastases. While the mutational status is mainly unaltered, epigenetic regulation is diverging. Based on methylome and transcriptome analyses of 16 matched intra- and extracranial metastases, 38 protein candidates with distinct promoter methylation and corresponding expression were identified. Eight promising candidates were validated by immunohistochemistry and had a significantly higher protein expression in intracranial metastases. (PMID: 36716920) In this study, we want to investigate the role of a likely cancer-promoting candidate, named protein kinase C zeta (PRKCz), which is upregulated in intracranial metastases. We found a wide range of PRKCz gene expression in various established as well as in-house patient-derived melanoma cell lines. Cell lines with either high or moderate PRKCz expression were chosen for further functional investigation. Using siRNA-mediated knockdown, a decreased viability was seen in PRKCz-knockdown cells in crystal violet assays. To test their role in migration, a 2D wound closure scratch assay was developed and revealed a decreased wound-closure capacity in PRKCz-knockdown cells. Further, PRKCz was found to regulate phosphorylated AKT, a component of the cancer-promoting PI3K/AKT signaling pathway, while phosphorylated ERK, a MAPK signaling component, remained unaffected. In summary, we have shown that PRKCz promotes cell viability and migration in melanoma cells. Melanoma brain metastases therefore benefit from high PRKCz levels in comparison to lower levels in extracranial metastases.
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pmc
