Hou Sheng-Mou, Cheng Ching-Yuan, Chen Wei-Li, Chang En-Ming, Lin Chih-Yang
Department of Research, Taiwan Blood Services Foundation, Taipei 111, Taiwan.
The Director's Office, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan.
Life (Basel). 2025 Jan 15;15(1):99. doi: 10.3390/life15010099.
Angiogenesis plays a critical role in osteosarcoma (OS) growth and metastasis. While nerve growth factor (NGF) is implicated in cancer progression, its role in OS angiogenesis remains unclear. This study explored NGF's effects on angiogenesis and the underlying molecular mechanisms. Analysis of GEO (GSE16088) data identified five angiogenesis markers significantly upregulated in OS tissues. In vitro experiments demonstrated that NGF enhanced HUVEC tube formation by upregulating platelet-derived growth factor C (PDGF-C) expression and suppressing microRNA-29b-3p (miR-29b-3p). The results of tube formation assays confirmed that NGF stimulation significantly increased the angiogenic capacity of MG63/NGF cells compared to MG63 cells. Furthermore, larotrectinib, a TrkA inhibitor, effectively reduced the migration and invasion abilities of MG63/NGF cells in a dose-dependent manner. These findings suggest that the NGF-TrkA axis promotes PDGF-C-mediated angiogenesis by inhibiting miR-29b-3p signaling. Larotrectinib could serve as a potential therapeutic agent targeting NGF-mediated angiogenesis in OS, offering a promising avenue for treatment.
血管生成在骨肉瘤（OS）的生长和转移中起关键作用。虽然神经生长因子（NGF）与癌症进展有关，但其在OS血管生成中的作用仍不清楚。本研究探讨了NGF对血管生成的影响及其潜在的分子机制。对GEO（GSE16088）数据的分析确定了在OS组织中显著上调的五个血管生成标志物。体外实验表明，NGF通过上调血小板衍生生长因子C（PDGF-C）的表达和抑制微小RNA-29b-3p（miR-29b-3p）来增强人脐静脉内皮细胞（HUVEC）的管腔形成。管腔形成实验结果证实，与MG63细胞相比，NGF刺激显著提高了MG63/NGF细胞的血管生成能力。此外，TrkA抑制剂拉罗替尼以剂量依赖的方式有效降低了MG63/NGF细胞的迁移和侵袭能力。这些发现表明，NGF-TrkA轴通过抑制miR-29b-3p信号通路促进PDGF-C介导的血管生成。拉罗替尼可作为一种潜在的治疗药物，靶向OS中NGF介导的血管生成，为治疗提供了一条有前景的途径。
