原代人肺成纤维细胞骨肉瘤外泌体诱导免疫调节和致瘤表型。

IF 2 Q3 ONCOLOGY

Cancer research communications Pub Date : 2025-04-01 DOI:10.1158/2767-9764.CRC-24-0371

Eric P Palmer, Kathryn E Cronise, Laurel A Haines, Sunetra Das, Aaron Offermann, Carina P Easton, Daniel P Regan

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引用次数: 0

摘要

骨肉瘤（Osteosarcoma， OS）是最常见的恶性骨癌。30-40%的OS患者发生肿瘤复发，几乎全部以肺转移的形式出现，这与20%的5年生存率有关。癌症相关成纤维细胞是肺TME中的一种关键细胞类型，促进免疫抑制、耐药和肿瘤细胞存活。先前的研究表明，肿瘤细胞可以通过外泌体介导的细胞间通讯，将成纤维细胞同化为促肿瘤表型。目前，OS外泌体调节常驻肺成纤维细胞功能的机制尚未得到评估。为了研究这一点，我们从6个OS细胞系中分离出外泌体。我们评估了人供体来源的原代肺成纤维细胞(LF’s；n=4)通过流式细胞术、共聚焦荧光显微镜、增殖试验、磷酸激酶阵列、多重细胞因子分析和rna测序，对体外处理的OS外泌体进行了研究。我们观察到，与未治疗的LFs相比，LFs有效地摄取OS外泌体，这与诱导MAPK通路激活、成纤维细胞增殖以及IL-6、CXCL8和CCL2分泌显著增强有关。外泌体处理的LFs的RNA-seq证实了这些反应，并发现与细胞因子分泌、增殖、免疫细胞趋化、迁移、促炎和促纤维化介质相关的途径显著富集。最后，在外泌体诱导的肺成纤维细胞-OS共培养模型中，与未处理的成纤维细胞相比，外泌体诱导的LFs显著提高了OS细胞的存活率和增殖能力。综上所述，这些数据表明OS来源的外泌体可以在肺成纤维细胞中诱导一种标志性的caf样炎症表型，为可能促进复发性OS肺转移的机制提供了有价值的见解。

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Osteosarcoma Exosome Priming of Primary Human Lung Fibroblasts Induces an Immune Modulatory and Protumorigenic Phenotype.

Significance: These findings provide a critical first step in characterizing the capacity of OS-derived exosomes to reprogram primary LFs toward a tumor-promoting inflammatory phenotype in vitro, offering novel molecular targets for the modulation of fibroblasts in the lung microenvironment as potential therapeutic strategies to prevent OS metastasis.

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Cancer research communications

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