Role of aldolase A in osteosarcoma progression and metastasis: In vitro and in vivo evidence

Long,Feng; Cai,Xinyan; Luo,Wei; Chen,Liang; Li,Kanghua

doi:10.3892/or.2014.3473

November-2014 Volume 32 Issue 5

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November-2014 Volume 32 Issue 5

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Article

Role of aldolase A in osteosarcoma progression and metastasis: In vitro and in vivo evidence

Authors:
- Feng Long
- Xinyan Cai
- Wei Luo
- Liang Chen
- Kanghua Li
View Affiliations / Copyright

Affiliations: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China, Department of Neonatology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China
Pages: 2031-2037
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Published online on: September 10, 2014

https://doi.org/10.3892/or.2014.3473
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Abstract

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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Role of aldolase A in osteosarcoma progression and metastasis: In vitro and in vivo evidence

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