Aims

Insulin-like growth factor (IGF) signaling has been documented in several human malignancies and is thought to contribute to cellular differentiation and migration, as well as malignant progression. A major binding molecule of IGF, IGF-binding protein 3 (IGFBP-3), regulates multiple IGF effects. Here, we focused on the effect of IGFBP-3 in the motility of osteosarcoma cells and examined signaling regulation.

Materials and methods

Using a human osteosarcoma tissue array, immunohistochemical staining determined levels of IGFBP-3 expression in osteosarcoma tissue and in normal tissue. The wound healing migration assay, Transwell migration assay, luciferase reporter assay, immunofluorescence staining, Western blot and real-time quantitative PCR were performed to examine whether IGFBP-3 facilitates VCAM-1-dependent migration of osteosarcoma cells.

Key findings

In this study, we found significantly higher IGFBP-3 levels in osteosarcoma tissue compared with normal healthy tissue. IGFBP-3 treatment of two human osteosarcoma cell lines promoted cell migration and upregulated levels of VCAM-1 expression via PI3K/Akt and AP-1 signaling.

Significance

IGFBP-3 appears to be a novel therapeutic target in metastatic osteosarcoma.

中文翻译：

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IGFBP-3通过上调VCAM-1表达来刺激人骨肉瘤细胞迁移

目的

胰岛素样生长因子（IGF）信号已在几种人类恶性肿瘤中得到记录，并被认为有助于细胞分化和迁移以及恶性进展。IGF的主要结合分子，即IGF结合蛋白3（IGFBP-3），调节多种IGF的作用。在这里，我们集中于IGFBP-3在骨肉瘤细胞运动中的作用，并检查了信号传导调节。

材料和方法

使用人骨肉瘤组织阵列，免疫组织化学染色确定了骨肉瘤组织和正常组织中IGFBP-3表达的水平。进行伤口愈合迁移测定，Transwell迁移测定，荧光素酶报告基因测定，免疫荧光染色，Western印迹和实时定量PCR，以检查IGFBP-3是否促进骨肉瘤细胞的VCAM-1依赖性迁移。

主要发现

在这项研究中，我们发现骨肉瘤组织中的IGFBP-3水平明显高于正常健康组织。IGFBP-3处理两种人骨肉瘤细胞系可通过PI3K / Akt和AP-1信号传导促进细胞迁移并上调VCAM-1表达水平。

意义

IGFBP-3似乎是转移性骨肉瘤中的新型治疗靶标。