Soluble AXL as a marker of disease progression and survival in melanoma


Autoři: Karine Flem-Karlsen aff001;  Marta Nyakas aff002;  Inger Nina Farstad aff001;  Erin McFadden aff001;  Patrik Wernhoff aff001;  Kari Dolven Jacobsen aff004;  Vivi Ann Flørenes aff001;  Gunhild Mari Mælandsmo aff003
Působiště autorů: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway aff001;  Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway aff002;  Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway aff003;  Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway aff004;  Institute of Medical Biology, Faculty of Health Sciences, UiT–Arctic University of Norway, Tromsø, Norway aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227187

Souhrn

Receptor tyrosine kinase AXL is a one-pass transmembrane protein upregulated in cancers and associated with lower survival and therapy resistance. AXL can be cleaved by the A Disintegrin and Metalloproteinases (ADAM)10 and ADAM17, yielding a soluble version of the protein. Elevated soluble AXL (sAXL) has been reported to be associated with disease progression in hepatocellular carcinoma, renal cancer, neurofibromatosis type 1 and inflammatory diseases. In the present work, we analyzed sAXL levels in blood from melanoma patients and showed that sAXL increases with disease progression. Additionally, increased sAXL levels were found correlated with shorter two-year survival in stage IV patients treated with ipilimumab. Furthermore, we showed that sAXL levels were related to the percentage of cells expressing AXL in resected melanoma lymph node metastases. This finding was verified in vitro, where sAXL levels in the cell media corresponded to AXL expression in the cells. AXL inhibition using the small-molecular inhibitor BGB324 reduced sAXL levels, while the cellular expression was elevated through increased protein stability. Our findings signify that quantification of sAXL blood levels is a simple and easily assessable method to determine cellular AXL levels and should be further evaluated for its use as a biomarker of disease progression and treatment response.

Klíčová slova:

Blood plasma – Cancer treatment – Enzyme-linked immunoassays – Immunohistochemistry techniques – Lymph nodes – Melanoma cells – Melanomas – Protein expression


Zdroje

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