Tumor-derived apoptotic extracellular vesicle-mediated intercellular communication promotes metastasis and stemness of lung adenocarcinoma.

Abstract

Apoptosis has long been recognized as a significant mechanism for inhibiting tumor formation, and a plethora of stimuli can induce apoptosis during the progression and treatment of tumors. Moreover, tumor-derived apoptotic extracellular vesicles (apoEVs) are inevitably phagocytosed by live tumor cells, promoting tumor heterogeneity. Understanding the mechanism by which apoEVs regulate tumor cells is imperative for enhancing our knowledge of tumor metastasis and recurrence. Herein, we conducted a series of in vivo and in vitro experiments, and we report that tumor-derived apoEVs promoted lung adenocarcinoma (LUAD) metastasis, self-renewal and chemoresistance. Mechanistically, we demonstrated that apoEVs facilitated tumor metastasis and stemness by initiating the epithelial-mesenchymal transition program and upregulating the transcription of the stem cell factor SOX2. In addition, we found that ALDH1A1, which was transported by apoEVs, activated the NF-κB signaling pathway by increasing aldehyde dehydrogenase enzyme activity in recipient tumor cells. Furthermore, targeting apoEVs-ALDH1A1 significantly abrogated these effects. Collectively, our findings elucidate a novel mechanism of apoEV-dependent intercellular communication between apoptotic tumor cells and live tumor cells that promotes the formation of cancer stem cell-like populations, and these findings reveal that apoEVs-ALDH1A1 may be a potential therapeutic target and biomarker for LUAD metastasis and recurrence.

• Authors: Xiaotian He, Yiyang Ma, Yingsheng Wen, Rusi Zhang, Dechang Zhao, Gongming Wang, Weidong Wang, Zirui Huang, Guangran Guo, Xuewen Zhang, Huayue Lin, Lanjun Zhang
• Journal: Bioactive materials (Bioact Mater) Vol. 36 Pg. 238-255 (Jun 2024) ISSN: 2452-199X [Electronic] China
• PMID: 38481566 (Publication Type: Journal Article)
• Copyright: © 2024 The Authors.