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Targeted Metabolomics Identifies Plasma Biomarkers in Mice with Metabolically Heterogeneous Melanoma Xenografts.
Weber, Daniela D; Thapa, Maheshwor; Aminzadeh-Gohari, Sepideh; Redtenbacher, Anna-Sophia; Catalano, Luca; Feichtinger, René G; Koelblinger, Peter; Dallmann, Guido; Emberger, Michael; Kofler, Barbara; Lang, Roland.
Afiliação
  • Weber DD; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.
  • Thapa M; BIOCRATES Life Sciences AG, 6020 Innsbruck, Austria.
  • Aminzadeh-Gohari S; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.
  • Redtenbacher AS; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.
  • Catalano L; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.
  • Feichtinger RG; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.
  • Koelblinger P; Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.
  • Dallmann G; BIOCRATES Life Sciences AG, 6020 Innsbruck, Austria.
  • Emberger M; Patholab Salzburg, 5020 Salzburg, Austria.
  • Kofler B; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.
  • Lang R; Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.
Cancers (Basel) ; 13(3)2021 Jan 23.
Article em En | MEDLINE | ID: mdl-33498757
ABSTRACT
Melanomas are genetically and metabolically heterogeneous, which influences therapeutic efficacy and contributes to the development of treatment resistance in patients with metastatic disease. Metabolite phenotyping helps to better understand complex metabolic diseases, such as melanoma, and facilitates the development of novel therapies. Our aim was to characterize the tumor and plasma metabolomes of mice bearing genetically different melanoma xenografts. We engrafted the human melanoma cell lines A375 (BRAF mutant), WM47 (BRAF mutant), WM3000 (NRAS mutant), and WM3311 (BRAF, NRAS, NF1 triple-wildtype) and performed a broad-spectrum targeted metabolomics analysis of tumor and plasma samples obtained from melanoma-bearing mice as well as plasma samples from healthy control mice. Differences in ceramide and phosphatidylcholine species were observed between melanoma subtypes irrespective of the genetic driver mutation. Furthermore, beta-alanine metabolism differed between melanoma subtypes and was significantly enriched in plasma from melanoma-bearing mice compared to healthy mice. Moreover, we identified beta-alanine, p-cresol sulfate, sarcosine, tiglylcarnitine, two dihexosylceramides, and one phosphatidylcholine as potential melanoma biomarkers in plasma. The present data reflect the metabolic heterogeneity of melanomas but also suggest a diagnostic biomarker signature for melanoma screening.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article