文章：

在肝黑色素瘤转移背景下Stabilin-1的缺乏研究

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

原文发布日期：19 January 2024

DOI: 10.3390/cancers16020441

类型: Article

开放获取: 是

英文摘要：

Background: This study analyzed the role of Stabilin-1 on hepatic melanoma metastasis in preclinical mouse models. Methods: InStabilin-1−/−mice (Stab1 KO), liver colonization of B16F10luc2and 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 B16F10luc2or Wt31 melanoma was unaltered between Stab1 KO and wildtype (Ctrl) mice, metastases of B16F10luc2tended 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 B16F10luc2model. 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 B16F10luc2model. Interestingly, significantly higher levels of POSTN were found in the matrix of hepatic metastases of Wt31, while liver metastases of B16F10luc2showed 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.

摘要翻译： 

背景：本研究在临床前小鼠模型中分析了Stabilin-1对肝脏黑色素瘤转移的作用。方法：在Stabilin-1基因敲除（Stab1 KO）小鼠中，观察B16F10luc2与Wt31黑色素瘤的肝脏定植情况。通过免疫荧光技术分析肝转移灶的数量、形态、血管化特征及肝脏微环境。结果：虽然B16F10luc2或Wt31黑色素瘤在Stab1 KO与野生型（Ctrl）小鼠间的肝转移率无显著差异，但B16F10luc2在Stab1 KO小鼠中的转移灶呈现缩小趋势。两类肝转移灶的内皮分化特征在Stab1 KO与Ctrl组间相似。在B16F10luc2模型中，未检测到肿瘤细胞在肝脏血管的初始黏附与滞留存在差异。免疫微环境分析显示，B16F10luc2模型中Stab1 KO组的CD45+Gr-1+细胞水平较Ctrl组有升高趋势。值得注意的是，Wt31肝转移灶基质中POSTN表达显著增高，而B16F10luc2肝转移灶则呈现RELN沉积增加的趋势。结论：肝脏黑色素瘤转移灶对靶向Stabilin-1的治疗策略表现出抵抗性，提示抗Stab1疗法需根据肿瘤实体类型或靶器官特性进行针对性考量。

原文链接：

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