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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Metastasis | Research

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

Authors: 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, Cyrill Géraud

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

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.
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Metadata
Title
Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment
Authors
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
Cyrill Géraud
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03255-4

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