Deficiency of Stabilin-1 in the Context of Hepatic Melanoma Metastasis

Sebastian A Wohlfeil; Ana Olsavszky; Anna Lena Irkens; Verena Häfele; Bianca Dietsch; Niklas Straub; Sergij Goerdt; Cyrill Géraud

doi:10.3390/cancers16020441

Deficiency of Stabilin-1 in the Context of Hepatic Melanoma Metastasis

Cancers (Basel). 2024 Jan 19;16(2):441. doi: 10.3390/cancers16020441.

Authors

Sebastian A Wohlfeil^{1

2

3}, Ana Olsavszky^{1

2}, Anna Lena Irkens^{1

2}, Verena Häfele^{1

2}, Bianca Dietsch^{1

2}, Niklas Straub^{1

2}, Sergij Goerdt^{1

4}, Cyrill Géraud^{1

2

4}

Affiliations

¹ Department of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, 68135 Mannheim, Germany.
² Section of Clinical and Molecular Dermatology, Medical Faculty Mannheim, Heidelberg University, 68135 Mannheim, Germany.
³ Skin Cancer Unit, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
⁴ European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, 68135 Mannheim, Germany.

Abstract

Background: This study analyzed the role of Stabilin-1 on hepatic melanoma metastasis in preclinical mouse models.

Methods: In Stabilin-1^-/- mice (Stab1 KO), liver colonization of B16F10 luc2 and Wt31 melanoma was investigated. The numbers, morphology, and vascularization of hepatic metastases and the hepatic microenvironment were analyzed by immunofluorescence.

Results: While hepatic metastasis of B16F10 luc2 or Wt31 melanoma was unaltered between Stab1 KO and wildtype (Ctrl) mice, metastases of B16F10 luc2 tended to be smaller in Stab1 KO. The endothelial differentiation of both types of liver metastases was similar in Stab1 KO and Ctrl. No differences in initial tumor cell adhesion and retention to the liver vasculature were detected in the B16F10 luc2 model. Analysis of the immune microenvironment revealed a trend towards higher levels of CD45⁺Gr-1⁺ cells in Stab1 KO as compared to Ctrl in the B16F10 luc2 model. Interestingly, significantly higher levels of POSTN were found in the matrix of hepatic metastases of Wt31, while liver metastases of B16F10 luc2 showed a trend towards increased deposition of RELN.

Conclusions: Hepatic melanoma metastases show resistance to Stabilin-1 targeting approaches. This suggests that anti-Stab1 therapies should be considered with respect to the tumor entity or target organs.

Keywords: Stablin-1; cutaneous melanoma; liver metastasis; melanoma metastasis; melanoma therapy.

Abstract

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