胶质母细胞瘤（GBM）以星形细胞​​肿瘤发生为特征，仍然是预后最具挑战性的肿瘤类型之一。使用新型治疗因子靶向整个 GBM 微环境是目前理想的研究方法。在这项研究中，我们重点关注颗粒体蛋白前体（PGRN），它是多种细胞功能的调节剂。最近的研究表明 PGRN 与 GBM 患者的不良预后有关。然而，PGRN 在 GBM 微环境中的具体作用仍然难以捉摸。我们利用 GBM 患者的公共数据库和以前的单细胞 RNA 序列来检查 PGRN 表达与患者生存/分级之间的关联，以及构成 GBM 微环境的每个细胞中 PGRN 的表达水平。肿瘤微环境。为了阐明 PGRN 在肿瘤相关巨噬细胞 (TAM) 中的作用，我们检测了当 PGRN 敲除 (Grn-/-) 或野生型小鼠的 TAM 来源的细胞上清液被处理时，小鼠 GBM 细胞中的细胞增殖和某些蛋白质的表达。鼠 GBM 细胞。我们的结果揭示了 GBM 环境中巨噬细胞中 PGRN 的显着表达，表明巨噬细胞中 PGRN 表达增加与肿瘤恶性肿瘤之间存在关联。 TAM 诱导导致 PGRN 表达增强。用 Grn-/- 小鼠骨髓源性巨噬细胞 (BMDM) 上清液处理导致 GBM 细胞增殖减少，细胞周期和间充质 GBM 亚型相关蛋白表达减少。此外，Grn-/-小鼠来源的BMDM上清液处理降低了GBM细胞中磷酸化STAT3的表达，而已知STAT3途径激活剂IL-6和IL-10的表达在Grn-/-小鼠来源的BMDM中减少。我们的结果表明，巨噬细胞衍生的 PGRN 对于促进肿瘤微环境中的恶性转化至关重要。© 2024。作者获得 Springer Science Business Media, LLC（Springer Nature 旗下子公司）的独家许可。

Glioblastoma (GBM), characterized by astrocytic tumorigenesis, remains one of the most prognostically challenging tumor types. Targeting entire GBM microenvironment using novel therapeutic factors is currently desired investigation approach. In this study, we focused on progranulin (PGRN), a regulator of diverse cellular functions. Recent studies implicated PGRN in the poor prognostics of GBM patients. However, the specific role of PGRN in the GBM microenvironment remains elusive.We utilized public databases of GBM patient and previous single-cell RNA sequence to examine association between PGRN expression and patient survival/grade, and expression levels of PGRN in each cell constituting the tumor microenvironment. To clarify the role of PGRN in Tumor-associated macrophage (TAM), we examined cell proliferation and expression of some proteins in murine GBM cells when cell supernatants derived from TAM of PGRN knockout (Grn-/-) or wild type mice were treated with murine GBM cells.Our results reveal significant PGRN expression in macrophages within the GBM environment, suggesting an association between increased PGRN expression in macrophages and tumor malignancy. TAM induction led to PGRN expression enhancement. Treatment with Grn-/- mouse -derived bone marrow-derived macrophage (BMDM) supernatant resulted in diminished GBM cell proliferation and cell cycle- and mesenchymal GBM subtype-associated reduced protein expression. Furthermore, the Grn-/- mouse-derived BMDM supernatant treatment reduced the phosphorylated STAT3 expression in GBM cells, while the expression of IL-6 and IL-10, known STAT3 pathway activators, diminished in Grn-/- mouse-derived BMDMs.Our results suggest that macrophage-derived PGRN is pivotal for fostering malignant transformations within the tumor microenvironment.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.