2. Academic Validation
  3. Vimentin intermediate filaments coordinate actin stress fibers and podosomes to determine the extracellular matrix degradation by macrophages

Vimentin intermediate filaments coordinate actin stress fibers and podosomes to determine the extracellular matrix degradation by macrophages

  • Dev Cell. 2025 Feb 7:S1534-5807(25)00036-X. doi: 10.1016/j.devcel.2025.01.016.
Xinyi Huang 1,  Zhifang Li 2,  Yuhan Huang 3,  Qian Zhang 2,  Yanqin Cui 4,  Xuemeng Shi 2,  Yaming Jiu 5
Affiliations

Affiliations

  • 1 Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China; Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China.
  • 2 Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China.
  • 3 Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, Beijing 100049, China.
  • 4 Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
  • 5 Unit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Yuquan Road No. 19(A), Shijingshan District, Beijing 100049, China. Electronic address: ymjiu@siii.cas.cn.
PMID: 39952241 DOI: 10.1016/j.devcel.2025.01.016
Abstract

Macrophages possess the capacity to degrade extracellular matrix (ECM), but the specific roles of different cytoskeletal structures in controlling this process are incompletely understood. Here, we report that the inward flow of actin stress fibers delivers endocytosed ECM for lysosomal elimination, replenishing the pool of Enzymes for extracellular ECM hydrolysis in actin-rich podosomes. Vimentin deficiency disrupted the balance between stress fibers and podosomes, impairing ECM degradation through Integrin CD11b in THP-1 macrophages. In lung adenocarcinoma patient samples, M2-type macrophages exhibit a tighter podosome organization, surrounded by compact vimentin filaments, than M1-type. In vitro experiments verified that the invasion ability of A549 lung carcinoma cells was enhanced when accompanied by wild type, but not vimentin knockout M2-type THP-1, macrophages. Subcutaneous injections of macrophages and tumor cells in nude mice showed that vimentin in macrophages can reduce tumor collagen fibers. Together, our findings provide insights into the cytoskeletal dynamics governing macrophage ECM degradation.

Keywords

CD11b; ECM degradation; actin filaments; cancer invasion; intermediate filaments; lung adenocarcinoma; macrophage; podosome; stress fibers; vimentin.

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