Li Yao, Zhao Yao, Shi Minghao, Ma Xiaoshan, Jia Mingbo, Shen Zhongjun, Liu Xiaoyi, Li Yunqian, Zhao Liyan
Department of Blood Transfusion, Second Hospital of Jilin University, Changchun, China.
Department of Neurosurgery, First Hospital of Jilin University, Changchun, China.
Cancer Med. 2025 Jun;14(12):e71002. doi: 10.1002/cam4.71002.
Platelet-derived growth factor-D (PDGF-D) is expressed at high levels in various tumors and is involved in epithelial-mesenchymal transition (EMT) and the malignant behavior of cancer cells. However, its role in glioma progression and the underlying molecular mechanisms remain unclear.
We used data from the Chinese Glioma Genome Atlas to evaluate the correlation among PDGF-D expression, tumor grade, and phenotype of glioma. The in situ expression of PDGF-D in clinical glioma specimens was analyzed through immunohistochemistry. Colony formation assays and transwell assays were performed for functional evaluation of glioma cell lines with PDGF-D knockdown or overexpression. Western blotting and RT-qPCR were conducted to explore molecular mechanisms.
PDGF-D was significantly upregulated in high-grade glioma and was associated with the malignant phenotype and poor prognosis. Knocking down PDGF-D in the LN18 glioma cell line reduced the expression of phosphorylated p65 and NOTCH1 and inhibited clonal proliferation, migration, invasion, and the EMT program. In contrast, inhibiting p65 phosphorylation in glioma cells overexpressing PDGF-D led to the downregulation of NOTCH1 and reversed EMT.
PDGF-D promotes the invasion and migration of glioma cells by activating the NF-κB/NOTCH1 pathway.
血小板衍生生长因子-D（PDGF-D）在多种肿瘤中高表达，参与上皮-间质转化（EMT）及癌细胞的恶性行为。然而，其在胶质瘤进展中的作用及潜在分子机制仍不清楚。
我们使用中国胶质瘤基因组图谱的数据来评估PDGF-D表达、肿瘤分级和胶质瘤表型之间的相关性。通过免疫组织化学分析临床胶质瘤标本中PDGF-D的原位表达。对PDGF-D敲低或过表达的胶质瘤细胞系进行集落形成试验和Transwell试验以进行功能评估。进行蛋白质免疫印迹法和逆转录定量聚合酶链反应以探索分子机制。
PDGF-D在高级别胶质瘤中显著上调，与恶性表型和不良预后相关。在LN18胶质瘤细胞系中敲低PDGF-D可降低磷酸化p65和NOTCH1的表达，并抑制克隆增殖、迁移、侵袭和EMT程序。相反，在过表达PDGF-D的胶质瘤细胞中抑制p65磷酸化导致NOTCH1下调并逆转EMT。
PDGF-D通过激活NF-κB/NOTCH1途径促进胶质瘤细胞的侵袭和迁移。
