Incliva Biomedical Health Research Institute, 46010 Valencia, Spain.
CIBER of Cancer (CIBERONC), 28029 Madrid, Spain.
Int J Mol Sci. 2024 Aug 10;25(16):8733. doi: 10.3390/ijms25168733.
Vitronectin is a glycoprotein present in plasma and the extracellular matrix that is implicated in cell migration. The high amount of vitronectin found in neuroblastoma biopsies has been associated with poor prognosis. Moreover, increased vitronectin levels have been described in the plasma of patients with different cancers. Our aim was to assess vitronectin as a potential circulating biomarker of neuroblastoma prognosis. Vitronectin concentration was quantified using ELISA in culture media of four neuroblastoma cell lines grown in a monolayer and in 3D models, and in the plasma of 114 neuroblastoma patients. Three of the neuroblastoma cell lines secreted vitronectin to culture media when cultured in a monolayer and 3D models. Vitronectin release was higher by neuroblastoma cells cultured in 3D models than in the monolayer and was still elevated when cells were grown in 3D scaffolds with cross-linked vitronectin. Vitronectin secretion occurred independently of cell numbers in cultures. Its concentration in the plasma of neuroblastoma patients ranged between 52.4 and 870 µg/mL (median, 218 µg/mL). A ROC curve was used to establish a cutoff of 361 µg/mL, above which patients over 18 months old had worse prognosis ( = 0.0018). Vitronectin could be considered a new plasma prognostic biomarker in neuroblastoma and warrants confirmation in collaborative studies. Drugs inhibiting vitronectin interactions with cells and/or the extracellular matrix could represent a significant improvement in survival for neuroblastoma patients.
纤连蛋白是一种存在于血浆和细胞外基质中的糖蛋白，与细胞迁移有关。神经母细胞瘤活检中发现的大量纤连蛋白与预后不良有关。此外，不同癌症患者的血浆中也描述了纤连蛋白水平的升高。我们的目的是评估纤连蛋白作为神经母细胞瘤预后的潜在循环生物标志物。使用 ELISA 定量检测了在单层和 3D 模型中培养的四个神经母细胞瘤细胞系的培养基中和 114 名神经母细胞瘤患者的血浆中的纤连蛋白浓度。当在单层和 3D 模型中培养时，有 3 种神经母细胞瘤细胞系分泌纤连蛋白到培养基中。与在单层中培养的神经母细胞瘤细胞相比，在 3D 模型中培养的神经母细胞瘤细胞释放的纤连蛋白更高，并且当细胞在交联纤连蛋白的 3D 支架中生长时，纤连蛋白的释放仍然升高。纤连蛋白的分泌与培养物中的细胞数量无关。神经母细胞瘤患者血浆中的浓度范围为 52.4 至 870 µg/mL（中位数为 218 µg/mL）。ROC 曲线用于建立 361 µg/mL 的截止值，超过该值的 18 个月以上的患者预后更差（=0.0018）。纤连蛋白可被认为是神经母细胞瘤的一种新的血浆预后生物标志物，需要在合作研究中得到证实。抑制纤连蛋白与细胞和/或细胞外基质相互作用的药物可能会显著改善神经母细胞瘤患者的生存率。
