Role of aldolase A in osteosarcoma progression and metastasis: In vitro and in vivo evidence
Role of aldolase A in osteosarcoma progression and metastasis: In vitro and in vivo evidence
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DOI：
10.3892/or.2014.3473
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发表时间：
2014-11-01
期刊：
影响因子：
4.2
通讯作者：
Li, Kanghua
中科院分区：
文献类型：
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作者：
Long, Feng;Cai, Xinyan;Li, Kanghua
醛缩酶A（ALDOA）是骨肉瘤（OS）的阴性生存标志物，可能与OS的发生和进展有关。在本研究中，我们首次评估了ALDOA在体外和体内OS细胞侵袭和存活中的功能作用，使用人OS细胞系和原位异种移植裸鼠模型。分别在MG-63和U-2 OS细胞中进行ALDOA的过表达和敲低，其分别显示相对低和高的组成型ALDOA表达水平。ALDOA在MG-63细胞中的过表达显著增加了体外细胞侵袭、基质金属蛋白酶（MMP）-2表达和细胞存活对抗顺铂诱导的凋亡。另一方面，ALDOA在U-2细胞中的敲低显著降低了体外细胞侵袭、MMP-2表达和顺铂诱导的细胞凋亡的细胞存活。在原位异种移植裸鼠模型中，胫骨内注射过表达ALDOA的MG-63细胞导致原发肿瘤体积和肺转移显著增加，原发肿瘤中的细胞凋亡减少。与此相反，胫骨内注射的U-2细胞与ALDOA敲低导致显着减少原发肿瘤体积和肺转移，以及增加细胞凋亡的原发肿瘤，与对照组相比。总之，我们的体外数据表明，ALDOA促进OS细胞的侵袭和存活，我们的体内数据表明，ALDOA在促进OS肿瘤生长和转移的重要作用。本研究提供了第一个在体外和体内的证据支持的关键功能作用的ALDOA在OS的进展和转移，表明ALDOA可以作为一个新的治疗靶点在OS。此外，我们的研究结果表明，ALDOA参与OS化疗耐药性的发展。
Aldolase A (ALDOA) has been reported to be negative survival marker of osteosarcoma (OS) and may be implicated in OS development and progression. In the present study, we assessed for the first time the functional role of ALDOA in OS cell invasion and survival in vitro and in vivo, using human OS cell lines and an orthotopic xenograft nude mouse model. Overexpression and knockdown of ALDOA were respectively performed in MG-63 and U-2 OS cells, which showed relatively low and high constitutive ALDOA expression levels, respectively. Overexpression of ALDOA in MG-63 cells significantly increased in vitro cell invasion, matrix metalloproteinase (MMP)-2 expression, and cell survival against cisplatin-induced apoptosis. On the other hand, knockdown of ALDOA in U-2 cells markedly decreased in vitro cell invasion, MMP-2 expression, and cell survival against cisplatin-induced apoptosis. In an orthotopic xenograft nude mouse model, intra-tibial injection of MG-63 cells overexpressing ALDOA led to significantly increased primary tumor volume and pulmonary metastasis as well as decreased cell apoptosis in the primary tumors, compared with the controls. In contrast, intra-tibial injection of U-2 cells with knockdown of ALDOA led to markedly decreased primary tumor volume and pulmonary metastasis as well as increased cell apoptosis in the primary tumors, compared with the controls. In conclusion, our in vitro data indicate that ALDOA promotes OS cell invasion and survival, and our in vivo data demonstrate an important role of ALDOA in promoting OS tumor growth and metastasis. The present study provides the first in vitro and in vivo evidence supporting a critical functional role of ALDOA in OS progression and metastasis, suggesting that ALDOA could serve as a novel therapeutic target in OS. Additionally, our results suggest that ALDOA is involved in the development of OS chemoresistance.