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<p>Exosome roles in cellular cross-talking within tumor microenvironment (TME) is a critical event in tumorigenesis. Type 2 macrophages (M2), cancer-associated fibroblasts (CAFs) and cancer stem cells (CSCs) are the three most important cells in cancer progression and metastasis, and targeting their connectome route can be an effective anti-cancer strategy. Exosomes mediate bidirectional cross-talking between the three cell types in which exosomes secreted from CSCs promote polarization of M2 macrophages and CAFs, and that M2- and CAF-derived exosomes promote cancer stemness through activation of epithelial-mesenchymal transition (EMT)-related signaling including transforming growth factor (TGF)-<i>β</i>, WNT/<i>β</i>-catenin and epidermal growth factor (EGF). CSC-derived exosomal TGF-<i>β</i> is a key driver of CAF and M2 macrophage polarization, with the latter mediated through activation of signal transducer and activator of transcription 3 (STAT3). <i>β</i>-catenin activity also seems to take important role in exosomal cross-talk between CAFs and stemness state of cancer. Incubation of exosomes with inhibitors of signaling inter-connecting CSCs, M2 and CAFs is a key anti-cancer strategy and a promising supplementary to the routine immunotherapeutic approaches in cancer therapy.</p>

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Exosomes in bridging macrophage-fibroblast polarity and cancer stemness

  • 期刊论文

  • 发表日期：

    2025年5月21日

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  • Keywan Mortezaee

摘要

Exosome roles in cellular cross-talking within tumor microenvironment (TME) is a critical event in tumorigenesis. Type 2 macrophages (M2), cancer-associated fibroblasts (CAFs) and cancer stem cells (CSCs) are the three most important cells in cancer progression and metastasis, and targeting their connectome route can be an effective anti-cancer strategy. Exosomes mediate bidirectional cross-talking between the three cell types in which exosomes secreted from CSCs promote polarization of M2 macrophages and CAFs, and that M2- and CAF-derived exosomes promote cancer stemness through activation of epithelial-mesenchymal transition (EMT)-related signaling including transforming growth factor (TGF)-β, WNT/β-catenin and epidermal growth factor (EGF). CSC-derived exosomal TGF-β is a key driver of CAF and M2 macrophage polarization, with the latter mediated through activation of signal transducer and activator of transcription 3 (STAT3). β-catenin activity also seems to take important role in exosomal cross-talk between CAFs and stemness state of cancer. Incubation of exosomes with inhibitors of signaling inter-connecting CSCs, M2 and CAFs is a key anti-cancer strategy and a promising supplementary to the routine immunotherapeutic approaches in cancer therapy.