Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment
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...
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03255-4 |
| _version_ | 1818500887798087680 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sebastian A. Wohlfeil |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T20:48:45Z |
| format | Article |
| id | doaj.art-01d951e23b144140b8554b9e1c7d0db6 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-10T20:48:45Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-01d951e23b144140b8554b9e1c7d0db62022-12-22T01:34:10ZengBMCJournal of Translational Medicine1479-58762022-02-0120111810.1186/s12967-022-03255-4Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatmentSebastian A. Wohlfeil0Verena Häfele1Bianca Dietsch2Céline Weller3Carsten Sticht4Anna Sophia Jauch5Manuel Winkler6Christian David Schmid7Anna Lena Irkens8Ana Olsavszky9Kai Schledzewski10Philipp-Sebastian Reiners-Koch11Sergij Goerdt12Cyrill Géraud13Department of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyNGS Core Facility, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyDepartment of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in DermatologyAbstract 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.https://doi.org/10.1186/s12967-022-03255-4Cutaneous melanomaMelanoma metastasisLiver metastasisTumor heterogeneityAnti-angiogenesisSorafenib |
| spellingShingle | 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 Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment Journal of Translational Medicine Cutaneous melanoma Melanoma metastasis Liver metastasis Tumor heterogeneity Anti-angiogenesis Sorafenib |
| title | Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment |
| title_full | Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment |
| title_fullStr | Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment |
| title_full_unstemmed | Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment |
| title_short | Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment |
| title_sort | angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti angiogenic treatment |
| topic | Cutaneous melanoma Melanoma metastasis Liver metastasis Tumor heterogeneity Anti-angiogenesis Sorafenib |
| url | https://doi.org/10.1186/s12967-022-03255-4 |
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