Abstract

Melanoma is a leading cause of high mortality that frequently spreads to the brain and is associated with deterioration in quality and quantity of life. Treatment opportunities have been restricted until now and new therapy options are urgently required. Our focus was to reveal the potential heterogeneity of melanoma brain metastasis. We succeeded to establish a brain melanoma metastasis cell line, namely MUG-Mel1 and two resulting clones D5 and C8 by morphological variety, differences in lipidome, growth behavior, surface, and stem cell markers. Mutation analysis by next-generation sequencing, copy number profiling, and cytogenetics demonstrated the different genetic profile of MUG-Mel1 and clones. Tumorigenicity was unsuccessfully tested in various mouse systems and finally established in a zebra fish model. As innovative treatment option, with high potential to pass the blood-brain barrier a peptide isolated from lactoferricin was studied in potential toxicity. Brain metastases are a major clinical challenge, therefore the development of relevant in vitro and in vivo models derived from brain melanoma metastases provides valuable information about tumor biology and offers great potential to screen for new innovative therapies.

Details

Title
Human melanoma brain metastases cell line MUG-Mel1, isolated clones and their detailed characterization
Author
Heitzer, Ellen 1   VIAFID ORCID Logo  ; Groenewoud Arwin 2 ; Meditz Katharina 3 ; Lohberger Birgit 4 ; Liegl-Atzwanger Bernadette 5 ; Prokesch Andreas 6   VIAFID ORCID Logo  ; Kashofer Karl 5 ; Behrens, Diana 7 ; Haybaeck Johannes 8   VIAFID ORCID Logo  ; Kolb-Lenz Dagmar 9 ; Koefeler Harald 10 ; Riedl, Sabrina 11 ; Schaider Helmut 12 ; Fischer, Carina 13 ; Ewa, Snaar-Jagalska B 2 ; de’Jong Danielle 14 ; Szuhai Karoly 14   VIAFID ORCID Logo  ; Zweytick Dagmar 11 ; Rinner Beate 3 

 Medical University of Graz, Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Graz, Austria (GRID:grid.11598.34) (ISNI:0000 0000 8988 2476) 
 Leiden University, Institute of Biology, Leiden, The Netherlands (GRID:grid.5132.5) (ISNI:0000 0001 2312 1970) 
 Medical University of Graz, Department for Biomedical Research, Graz, Austria (GRID:grid.11598.34) (ISNI:0000 0000 8988 2476) 
 Medical University of Graz, Department of Orthopedics and Trauma, Graz, Austria (GRID:grid.11598.34) (ISNI:0000 0000 8988 2476) 
 Medical University of Graz, Institute of Pathology, Graz, Austria (GRID:grid.11598.34) (ISNI:0000 0000 8988 2476) 
 Metabolism & Aging, Medical University of Graz, Gottfried Schatz Research Center for Cell Signaling, Graz, Austria (GRID:grid.11598.34) (ISNI:0000 0000 8988 2476); BioTechMed-Graz, Graz, Austria (GRID:grid.452216.6) 
 EPO - Experimental Pharmacology and Oncology GmbH, Berlin, Germany (GRID:grid.11598.34) 
 Medical University of Graz, Institute of Pathology, Graz, Austria (GRID:grid.11598.34) (ISNI:0000 0000 8988 2476); Otto von Guericke University Magdeburg, Department of Pathology, Medical Faculty, Magdeburg, Germany (GRID:grid.5807.a) (ISNI:0000 0001 1018 4307) 
 Metabolism & Aging, Medical University of Graz, Gottfried Schatz Research Center for Cell Signaling, Graz, Austria (GRID:grid.11598.34) (ISNI:0000 0000 8988 2476); Medical University of Graz, Center for Medical Research, Graz, Austria (GRID:grid.11598.34) (ISNI:0000 0000 8988 2476) 
10  Medical University of Graz, Center for Medical Research, Graz, Austria (GRID:grid.11598.34) (ISNI:0000 0000 8988 2476) 
11  University of Graz, Institute of Molecular Biosciences, Biophysics Division, Graz, Austria (GRID:grid.5110.5) (ISNI:0000000121539003) 
12  The University of Queensland, Dermatology Research Centre, Translational Research Institute, School of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
13  Red Cross Transfusion Service for Upper Austria, Graz, Austria (GRID:grid.1003.2) 
14  Department of Cell and Chemical Biology, LUMC, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2190112766
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.