治疗恶性胶质母细胞瘤（GBM）面临的一个重要挑战是其高侵袭性，促进细胞在整个大脑中的迁移，阻碍手术切除和有效药物输送。GBM细胞在接受目前金标准放疗（RT）和伴随和辅助替莫唑胺（TMZ）的治疗后表现出增强的侵袭能力，导致疾病迅速复发。阐明治疗后侵袭性GBM细胞使用的机制对于开发更有效的治疗方法至关重要。在本研究中，我们利用Nanostring®癌症进展基因表达面板识别出在临床相关剂量的RT/TMZ治疗后可能参与增强GBM细胞侵袭的候选基因。我们的研究结果确定了血栓调节蛋白-1（THBS1）作为一种促侵袭基因，在这些细胞中上调。免疫荧光染色显示THBS1位于GBM细胞表面形成的功能性基质降解侵袭极点。此外，THBS1的过表达导致GBM细胞迁移和MMP-2的分泌增强，而THBS1的沉默减少了MMP-2的分泌。初步数据表明THBS1与GBM细胞中的侵袭极点相关，并可能参与RT/TMZ治疗后GBM细胞的侵袭过程。应进一步研究治疗性抑制THBS1介导的侵袭极点活性，以提高GBM细胞的侵袭，作为治疗GBM的方法。版权所有©2023，由Elsevier Inc.发表。

A critical challenge in the treatment of glioblastoma (GBM) is its highly invasive nature which promotes cell migration throughout the brain and hinders surgical resection and effective drug delivery. GBM cells demonstrate augmented invasive capabilities following exposure to current gold standard treatment of radiotherapy (RT) and concomitant and adjuvant temozolomide (TMZ), resulting in the rapid disease recurrence. Elucidating the mechanisms employed by post-treatment invasive GBM cells is critical to the development of more effective therapies. In this study we utilized a Nanostring® Cancer Progression gene expression panel to identify candidate genes that may be involved in enhanced GBM cell invasion after treatment with clinically relevant doses of RT/TMZ. Our findings identified thrombospondin-1 (THBS1) as a pro-invasive gene that is upregulated in these cells. Immunofluorescence staining revealed that THBS1 localised within functional matrix-degrading invadopodia that formed on the surface of GBM cells. Furthermore, overexpression of THBS1 resulted in enhanced GBM cell migration and secretion of MMP-2, which was reduced with silencing of THBS1. The preliminary data demonstrates that THBS1 is associated with invadopodia in GBM cells and is likely involved in the invadopodia-mediated invasive process in GBM cells exposed to RT/TMZ treatment. Therapeutic inhibition of THBS1-mediated invadopodia activity, which facilitates GBM cell invasion, should be further investigated as a treatment for GBM.Copyright © 2023. Published by Elsevier Inc.