Colon cancer exosome-associated HSP90B1 initiates pre-metastatic niche formation in the liver by polarizing M1 macrophage into M2 phenotype

被引：0

作者：

ShuJie Li ^{[1
]}

Xue Fu ^{[1
]}

Deng Ning ^{[2
]}

QiuMeng Liu ^{[3
]}

JunFang Zhao ^{[4
]}

Qi Cheng ^{[1
]}

XiaoPing Chen ^{[3
]}

Li Jiang ^{[4
]}

机构：

[1] Department of Biliary-Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan

[2] Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan

[3] Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Hubei, Wuhan

[4] Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan

[5] Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Ministry of Education, National Health Commission, Chinese Academy of Medical Sciences, Hubei, Wuhan

来源：

Biology Direct | / 20卷 / 1期

基金：

中国国家自然科学基金;

关键词：

Colon cancer; Exosome; HSP90B1; Macrophage polarization; Pre-metastatic Nich;

D O I：

10.1186/s13062-025-00623-0

中图分类号：

学科分类号：

摘要：

Background: Colorectal cancer (CRC) frequently metastasizes to the liver, worsening patient outcomes. The formation of a pre-metastatic niche (PMN) is essential for this process, but how the primary colon tumor orchestrates the PMN formation remains unclear. Methods: This study investigated the role of CRC-derived exosomes using CT-26 murine colon carcinoma cells. The effects of these exosomes on immune cells, specifically M1 macrophage polarization and CD8 + T cell viability, were assessed. HSP90B1 expression in CT-26-derived exosomes was analyzed to understand its contribution to PMN formation. HSP90B1 silencing experiments were conducted to evaluate its impact on immunosuppressive PMN creation and liver metastasis. Patient blood samples were also examined to correlate exosomal HSP90B1 levels with CRC progression. Results: Exosomes from CT-26 cells were found to polarize M1 macrophages into an M2 phenotype and decrease CD8 + T cell viability, promoting liver metastasis. High expression of HSP90B1 in CT-26 cell-derived exosomes was identified as a key factor in inducing M2 macrophage polarization and creating an immunosuppressive PMN. Silencing HSP90B1 significantly inhibited the exosome-mediated formation of the immunosuppressive PMN and reduced liver metastasis. Furthermore, elevated levels of HSP90B1 in patient-derived exosomes were associated with advanced CRC and poorer prognosis. Conclusions: CRC-derived exosomes promote liver metastasis by forming an immunosuppressive PMN through HSP90B1. Targeting HSP90B1 in CRC exosomes may offer a new therapeutic strategy to prevent liver metastasis and improve patient outcomes. © The Author(s) 2025.

引用

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