肝脏黑色素瘤转移背景下Stabilin-1的缺乏

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

作者信息

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

机构信息

Department of Dermatology, Venereology, and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, 68135 Mannheim, Germany.

Section of Clinical and Molecular Dermatology, Medical Faculty Mannheim, Heidelberg University, 68135 Mannheim, Germany.

出版信息

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

DOI:10.3390/cancers16020441

PMID:38275881

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10814973/

Abstract

BACKGROUND

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

METHODS

In mice (Stab1 KO), liver colonization of B16F10 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 or Wt31 melanoma was unaltered between Stab1 KO and wildtype (Ctrl) mice, metastases of B16F10 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 model. Analysis of the immune microenvironment revealed a trend towards higher levels of CD45Gr-1 cells in Stab1 KO as compared to Ctrl in the B16F10 model. Interestingly, significantly higher levels of POSTN were found in the matrix of hepatic metastases of Wt31, while liver metastases of B16F10 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.

摘要

背景

本研究在临床前小鼠模型中分析了稳定素-1对肝脏黑色素瘤转移的作用。

方法

在小鼠（Stab1基因敲除小鼠）中，研究了B16F10和Wt31黑色素瘤的肝脏定植情况。通过免疫荧光分析肝转移灶的数量、形态、血管生成以及肝脏微环境。

结果

虽然在Stab1基因敲除小鼠和野生型（对照）小鼠之间，B16F10或Wt31黑色素瘤的肝转移情况未发生改变，但在Stab1基因敲除小鼠中，B16F10的转移灶往往较小。在Stab1基因敲除小鼠和对照小鼠中，两种类型肝转移灶的内皮分化相似。在B16F10模型中，未检测到初始肿瘤细胞与肝脏血管系统的黏附及滞留存在差异。对免疫微环境的分析显示，在B16F10模型中，与对照相比，Stab1基因敲除小鼠中CD45Gr-1细胞水平有升高趋势。有趣的是，在Wt31肝转移灶的基质中发现POSTN水平显著更高，而B16F10的肝转移灶则显示RELN沉积有增加趋势。