Scholarlink

<p>Lung adenocarcinoma (LA) ranks among the most common malignant tumors worldwide. M2 macrophage-derived exosomes have been implicated in regulating LA progression and drug resistance. However, whether proteins encapsulated in these exosomes contribute to gefitinib resistance in LA remains to be elucidated. This study investigates the role of tissue inhibitor of metalloproteinase 1 (TIMP1) in mediating LA resistance to gefitinib. We demonstrated that M2 macrophages-derived exosomes enhanced the sensitivity of gefitinib-resistant LA cell lines (<i>P</i> &lt; 0.05). Bioinformatics analyses validated the correlation of TIMP1 expression with LA progression and patient survival. Depletion of TIMP1 in M2 macrophage-derived exosomes suppressed the proliferation of gefitinib-resistant LA cells. Additionally, we confirmed that TIMP1 interacts with cluster of differentiation 74 (CD74), a process linked to the proliferation and migration of gefitinib-resistant LA cells. Additionally, this study validated that TIMP1 mediates the interaction between CD74 and macrophage migration inhibitory factor (MIF), potentially activating the PI3K/AKT signaling pathway. Collectively, these findings demonstrate that TIMP1 in M2 macrophage-derived exosomes facilitate the binding of MIF to CD74 in LA cells, thereby attenuating gefitinib resistance.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月5日

查看全文
  • Jingcui Peng,
  • Yan Zhang,
  • Bin Li,
  • Xin He,
  • Cuimin Ding,
  • Wenxia Hu

摘要

Lung adenocarcinoma (LA) ranks among the most common malignant tumors worldwide. M2 macrophage-derived exosomes have been implicated in regulating LA progression and drug resistance. However, whether proteins encapsulated in these exosomes contribute to gefitinib resistance in LA remains to be elucidated. This study investigates the role of tissue inhibitor of metalloproteinase 1 (TIMP1) in mediating LA resistance to gefitinib. We demonstrated that M2 macrophages-derived exosomes enhanced the sensitivity of gefitinib-resistant LA cell lines (P < 0.05). Bioinformatics analyses validated the correlation of TIMP1 expression with LA progression and patient survival. Depletion of TIMP1 in M2 macrophage-derived exosomes suppressed the proliferation of gefitinib-resistant LA cells. Additionally, we confirmed that TIMP1 interacts with cluster of differentiation 74 (CD74), a process linked to the proliferation and migration of gefitinib-resistant LA cells. Additionally, this study validated that TIMP1 mediates the interaction between CD74 and macrophage migration inhibitory factor (MIF), potentially activating the PI3K/AKT signaling pathway. Collectively, these findings demonstrate that TIMP1 in M2 macrophage-derived exosomes facilitate the binding of MIF to CD74 in LA cells, thereby attenuating gefitinib resistance.