First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Cancer Biol Ther. 2011 Sep 15;12(6):539-48. doi: 10.4161/cbt.12.6.16301.
Astrocyte elevated gene-1 (AEG-1) is overexpressed in several cancers and plays an important role in cancer progression. However, AEG-1 expression, biological function, and clinical significance in osteosarcoma have not been uncovered. Utilizing manipulated human osteosarcoma cell lines and osteosarcoma tissues, we found that increasing expression of AEG-1 enhanced osteosarcoma cell proliferation and invasion in vitro, and knockdown of AEG-1 significantly attenuated osteosarcoma cell malignancy. Moreover, AEG-1 was overexpressed in osteosarcoma tissues, and overexpression of AEG-1 was strongly associated with gender (p = 0.018), clinical stages (p < 0.001), classification (p < 0.001), metastasis (p = 0.013), differentiation (p < 0.001), and poor survival (p = 0.021). Mechanistic studies conducted in vitro and in vivo revealed that AEG-1-mediated carcinogenesis and invasiveness might be through upregulating MMP-2. Taken together, our data strongly suggest that AEG-1 plays a crucial role in osteosarcoma progression through MMP-2, and AEG-1 could be a useful biomarker for the prediction of osteosarcoma progression and prognosis.
星形细胞上调基因-1（AEG-1）在多种癌症中过表达，在癌症进展中发挥重要作用。然而，AEG-1 在骨肉瘤中的表达、生物学功能和临床意义尚未被揭示。利用操纵的人骨肉瘤细胞系和骨肉瘤组织，我们发现增加 AEG-1 的表达可增强骨肉瘤细胞在体外的增殖和侵袭能力，而敲低 AEG-1 则显著减弱骨肉瘤细胞的恶性程度。此外，AEG-1 在骨肉瘤组织中过表达，并且 AEG-1 的过表达与性别（p = 0.018）、临床分期（p < 0.001）、分类（p < 0.001）、转移（p = 0.013）、分化（p < 0.001）和不良预后（p = 0.021）强烈相关。体外和体内的机制研究表明，AEG-1 介导的致癌作用和侵袭性可能是通过上调 MMP-2 实现的。总之，我们的数据强烈表明，AEG-1 通过 MMP-2 在骨肉瘤进展中发挥关键作用，AEG-1 可能成为预测骨肉瘤进展和预后的有用生物标志物。
