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Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment

BACKGROUND: Cutaneous melanoma exhibits heterogeneous metastatic patterns and prognosis. In this regard, liver metastasis, which is detected in ~ 10-20% of stage 4 patients, came to the fore of melanoma research, as it recently evolved as decisive indicator of treatment resistance to immune checkpoi...

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Main Authors: Wohlfeil, Sebastian A. (Author) , Häfele, Verena (Author) , Dietsch, Bianca (Author) , Weller, Céline (Author) , Sticht, Carsten (Author) , Jauch, Anna Sophia (Author) , Winkler, Manuel (Author) , Schmid, Christian David (Author) , Irkens, Anna Lena (Author) , Olsavszky, Ana (Author) , Schledzewski, Kai (Author) , Reiners-Koch, Philipp-Sebastian (Author) , Goerdt, Sergij (Author) , Géraud, Cyrill (Author)
Format: Article (Journal)
Language:English
Published: 02 February 2022
In: Journal of translational medicine
Year: 2022, Volume: 20, Pages: 1-18
ISSN:1479-5876
DOI:10.1186/s12967-022-03255-4
Online Access:Resolving-System, kostenfrei, Volltext: https://doi.org/10.1186/s12967-022-03255-4
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Author Notes:Sebastian A. Wohlfeil, Verena Häfele, Bianca Dietsch, Céline Weller, Carsten Sticht, Anna Sophia Jauch, Manuel Winkler, Christian David Schmid, Anna Lena Irkens, Ana Olsavszky, Kai Schledzewski, Philipp-Sebastian Reiners-Koch, Sergij Goerdt and Cyrill Géraud
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Summary:BACKGROUND: Cutaneous melanoma exhibits heterogeneous metastatic patterns and prognosis. In this regard, liver metastasis, which is detected in ~ 10-20% of stage 4 patients, came to the fore of melanoma research, as it recently evolved as decisive indicator of treatment resistance to immune checkpoint inhibition. - METHODS: Hepatic metastases were induced by intrasplenic injection of five different murine melanoma cell lines. The efficiencies of hepatic colonization, morphologic patterns, gene expression profiles and degree of vascularization were analyzed and Sorafenib was applied as anti-angiogenic treatment. - RESULTS: WT31 melanoma showed the highest efficiency of hepatic colonization, while intermediate efficiencies were observed for B16F10 and RET, and low efficiencies for D4M and HCmel12. RNAseq-based gene expression profiles of high and intermediate metastatic melanomas in comparison to low metastatic melanomas indicated that this efficiency predominantly associates with gene clusters involved in cell migration and angiogenesis. Indeed, heterogeneous vascularization patterns were found in the five models. Although the degree of vascularization of WT31 and B16F10 metastases differed, both showed a strong response to Sorafenib with a successful abrogation of the vascularization. - CONCLUSION: Our data indicate that molecular heterogeneity of melanomas can be associated with phenotypic and prognostic features of hepatic metastasis paving the way for organ-specific anti-angiogenic therapeutic approaches.
Item Description:Gesehen am 07.02.2022
Physical Description:Online Resource
ISSN:1479-5876
DOI:10.1186/s12967-022-03255-4

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