胶质母细胞瘤（GBM）是一种高度恶性且致命的脑瘤，平均生存时间不到12个月。已有多项研究表明，Claudin-3（CLDN3）在多种癌症中过度表达，并可能在其生长和扩散中具有重要作用。本研究使用了qRT-PCR、蛋白质免疫印迹、免疫组织化学和免疫荧光染色等方法，研究了各种蛋白质的表达水平。为了探索GBM细胞的增殖能力，我们进行了CCK-8和EdU-DNA形成实验。采用划痕愈合和Transwell实验来研究GBM细胞的侵袭和迁移能力。此外，我们构建了一个GBM颅内异种移植模型来研究CLDN3在体内的作用。本研究致力于研究CLDN3在GBM的发病机制和进展中的功能。我们的研究发现在GBM中CLDN3表达上调，可以刺激肿瘤细胞的生长和上皮间质转化（EMT），这一发现在实验室和动物模型中得到了验证。我们还发现，CLDN3表达可以由转化生长因子-β（TGF-β）引发，并通过TGF-β信号通路的特异性抑制剂ITD-1得到减少。进一步的分析揭示，CLDN3水平的增加增强了TGF-β诱导的GBM细胞的生长和EMT，而降低CLDN3水平则削弱了这些效应。我们的研究证明了CLDN3在促进GBM生长和转移中的功能，并显示其参与了TGF-β的肿瘤发生影响。因此，开发针对CLDN3的特异性抑制剂可能代表了治疗这种破坏性疾病的一种有前景的新方法。

Glioblastoma multiforme (GBM) is a significantly malignant and lethal brain tumor with an average survival time of less than 12 months. Several researches had shown that Claudin-3 (CLDN3) is overexpressed in various cancers and might be important in their growth and spread. In this study, we used qRT-PCR, western blotting, immunohistochemistry, and immunofluorescence staining assays to investigate the expression levels of various proteins. To explore the proliferation abilities of GBM cells, we conducted the CCK-8 and EdU-DNA formation assays. Wound healing and transwell assays were used to investigate the capacities of invasion and migration of GBM cells. Additionally, we constructed an intracranial xenograft model of GBM to study the in vivo role of CLDN3. Our study devoted to investigate the function of CLDN3 in the pathogenesis and progression of GBM. Our study revealed that CLDN3 was upregulated in GBM and could stimulate tumor cell growth and epithelial-mesenchymal transition (EMT) in both laboratory and animal models. We also discovered that CLDN3 expression could be triggered by transforming growth factor-β (TGF-β) and reduced by specific inhibitors of the TGF-β signaling pathway, such as ITD-1. Further analysis revealed that increased CLDN3 levels enhanced TGF-β-induced growth and EMT in GBM cells, while reducing CLDN3 levels weakened these effects. Our study demonstrated the function of CLDN3 in facilitating GBM growth and metastasis and indicated its involvement in the tumorigenic effects of TGF-β. Developing specific inhibitors of CLDN3 might, therefore, represent a promising new approach for treating this devastating disease.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.