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The inhibitory effect of M2 macrophage-derived exosomes on gefitinib resistant lung adenocarcinoma cells through the MIF/TIMP1/CD74 axis

  • 0Department of Respiratory Medicine, The Fourth Hospital of Hebei Medical University, NO. 12 Jiankang Road, Shijiazhuang, 050000, Hebei, China.
Scientific Reports +

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August 4, 2025

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August 4, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Tissue inhibitor of metalloproteinase 1 (TIMP1) in M2 macrophage exosomes can overcome gefitinib resistance in lung adenocarcinoma (LA). TIMP1 facilitates MIF-CD74 binding, enhancing LA cell sensitivity to gefitinib treatment.

Area Of Science

  • Oncology
  • Cell Biology
  • Biochemistry

Background

  • Lung adenocarcinoma (LA) is a prevalent cancer globally.
  • M2 macrophage-derived exosomes influence LA progression and drug resistance.
  • The role of exosomal proteins in gefitinib resistance is not fully understood.

Purpose Of The Study

  • To investigate the role of tissue inhibitor of metalloproteinase 1 (TIMP1) in mediating gefitinib resistance in LA.
  • To explore the interaction of TIMP1 with other molecules in this process.
  • To understand the underlying molecular mechanisms.

Main Methods

  • Analysis of M2 macrophage-derived exosomes and their effect on LA cell lines.
  • Bioinformatics analysis of TIMP1 expression in LA.
  • TIMP1 depletion experiments.
  • Co-immunoprecipitation assays to study protein interactions.
  • Western blotting to assess signaling pathways.

Main Results

  • M2 macrophage-derived exosomes increased gefitinib sensitivity in resistant LA cells.
  • TIMP1 expression correlates with LA progression and patient survival.
  • TIMP1 depletion in exosomes reduced proliferation of gefitinib-resistant LA cells.
  • TIMP1 interacts with CD74, affecting LA cell proliferation and migration.
  • TIMP1 mediates the interaction between MIF and CD74, activating the PI3K/AKT pathway.

Conclusions

  • TIMP1 within M2 macrophage-derived exosomes plays a critical role in gefitinib resistance in LA.
  • TIMP1 facilitates MIF-CD74 binding, leading to PI3K/AKT pathway activation.
  • Targeting TIMP1 may represent a therapeutic strategy to overcome gefitinib resistance in LA.

Keywords:

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