Lysophosphatidic acid acyltransferase β (LPAATβ) promotes the tumor growth of human osteosarcoma.

Abstract

BACKGROUND:

Osteosarcoma is the most common primary malignancy of bone with poorly characterized molecular pathways important in its pathogenesis. Increasing evidence indicates that elevated lipid biosynthesis is a characteristic feature of cancer. We sought to investigate the role of lysophosphatidic acid acyltransferase β (LPAATβ, aka, AGPAT2) in regulating the proliferation and growth of human osteosarcoma cells. LPAATβ can generate phosphatidic acid, which plays a key role in lipid biosynthesis as well as in cell proliferation and survival. Although elevated expression of LPAATβ has been reported in several types of human tumors, the role of LPAATβ in osteosarcoma progression has yet to be elucidated.

METHODOLOGY/PRINCIPAL FINDINGS:

Endogenous expression of LPAATβ in osteosarcoma cell lines is analyzed by using semi-quantitative PCR and immunohistochemical staining. Adenovirus-mediated overexpression of LPAATβ and silencing LPAATβ expression is employed to determine the effect of LPAATβ on osteosarcoma cell proliferation and migration in vitro and osteosarcoma tumor growth in vivo. We have found that expression of LPAATβ is readily detected in 8 of the 10 analyzed human osteosarcoma lines. Exogenous expression of LPAATβ promotes osteosarcoma cell proliferation and migration, while silencing LPAATβ expression inhibits these cellular characteristics. We further demonstrate that exogenous expression of LPAATβ effectively promotes tumor growth, while knockdown of LPAATβ expression inhibits tumor growth in an orthotopic xenograft model of human osteosarcoma.

CONCLUSIONS/SIGNIFICANCE:

Our results strongly suggest that LPAATβ expression may be associated with the aggressive phenotypes of human osteosarcoma and that LPAATβ may play an important role in regulating osteosarcoma cell proliferation and tumor growth. Thus, targeting LPAATβ may be exploited as a novel therapeutic strategy for the clinical management of osteosarcoma. This is especially attractive given the availability of selective pharmacological inhibitors.

• Authors: Farbod Rastegar, Jian-Li Gao, Deana Shenaq, Qing Luo, Qiong Shi, Stephanie H Kim, Wei Jiang, Eric R Wagner, Enyi Huang, Yanhong Gao, Jikun Shen, Ke Yang, Bai-Cheng He, Liang Chen, Guo-Wei Zuo, Jinyong Luo, Xiaoji Luo, Yang Bi, Xing Liu, Mi Li, Ning Hu, Linyuan Wang, Gaurav Luther, Hue H Luu, Rex C Haydon, Tong-Chuan He
• Journal: PloS one (PLoS One) Vol. 5 Issue 12 Pg. e14182 (Dec 01 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 21152068 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Lipids
• Tetrazolium Salts
• Thiazoles
• Acyltransferases
• 2-acylglycerophosphate acyltransferase
• thiazolyl blue
• Gentian Violet

Topics

• Acyltransferases (metabolism)
• Bone Neoplasms (metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Cell Survival
• Disease Progression
• Gene Expression Regulation, Neoplastic
• Gentian Violet (pharmacology)
• Humans
• Lipids (chemistry)
• Neoplasm Metastasis
• Osteosarcoma (metabolism)
• Phenotype
• Reverse Transcriptase Polymerase Chain Reaction
• Tetrazolium Salts (pharmacology)
• Thiazoles (pharmacology)