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  3. Colorectal cancer-derived extracellular vesicles containing HSP70 enhance macrophage phagocytosis by up-regulating MARCO expression

Colorectal cancer-derived extracellular vesicles containing HSP70 enhance macrophage phagocytosis by up-regulating MARCO expression

  • Exp Cell Res. 2023 Mar 22;426(2):113565. doi: 10.1016/j.yexcr.2023.113565.
Yu Sun 1,  Wenjun Xiao 2,  Yang Yu 2,  Yuchen Jiang 2,  Zhijie Xiao 2,  Defa Huang 3,  Tianyu Zhong 3,  Jiang Li 2,  Xi Xiang 2,  Yulong He 4,  Zhigang Li 5
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Digestive Cancer Research; Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China; Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
  • 2 Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
  • 3 Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province, 341004, China.
  • 4 Guangdong Provincial Key Laboratory of Digestive Cancer Research; Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China; Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. Electronic address: heyulong@mail.sysu.edu.cn.
  • 5 Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China; Shenzhen Key Laboratory of Chinese Medicine Active substance screening and Translational Research, Shenzhen, 518107, China. Electronic address: lizhg25@mail.sysu.edu.cn.
PMID: 36958650 DOI: 10.1016/j.yexcr.2023.113565
Abstract

In recent years, we have realized that extracellular vesicles (EVs) play a critical role in regulating the intercellular communication between tumor and immune cells in the tumor microenvironment (TME). Tumor-derived extracellular vesicles (TDEVs) profoundly affect the functional changes of tumor-associated macrophages (TAMs) and promote their M2 polarization. Meanwhile, macrophages have a strong phagocytic ability in phagocytosing apoptotic cells. Especially in the course of chemotherapy or radiotherapy, TAMs can phagocytose and remove apoptotic tumor cells, showing anti-inflammatory and pro-tumor effects. However, the underlying mechanisms by which TDEVs regulate macrophage phagocytosis of apoptotic tumor cells have not been fully elucidated. In this study, we focused on the effect of colorectal cancer-derived extracellular vesicles (CRC-EVs) on macrophages. We demonstrated that CRC-EVs enhanced macrophage phagocytosis of apoptotic CRC cells. We then determined that heat shock protein 70 (HSP70) carried in CRC-EVs was responsible for this effect by using mass spectrometry-based proteomic analysis and the CRISPR-Cas9 system. Through transcriptome Sequencing of macrophages, we found that the enhanced phagocytosis of macrophages was mainly due to the up-regulation of the macrophage receptor with collagenous structure (MARCO). In addition, we confirmed that the up-regulation of MARCO was mediated by the AKT-STAT3 signaling pathway. Taken together, this study revealed a novel EVs-mediated macrophage phagocytosis mechanism involved in the clearance of apoptotic tumor cells in the TME. Targeting TDEVs may have potential therapeutic applications in tumor treatment.

Keywords

Colorectal cancer; Extracellular vesicles; HSP70; MARCO; Macrophage; Phagocytosis.

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