Lysophosphatidic acid acyltransferase ß (LPAATß) 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 ß (LPAATß, aka, AGPAT2) in regulating the proliferation and growth of human osteosarcoma cells. LPAATß can generate phosphatidic acid, which plays a key role in lipid biosynthesis as well as in cell proliferation and survival. Although elevated expression of LPAATß has been reported in several types of human tumors, the role of LPAATß in osteosarcoma progression has yet to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Endogenous expression of LPAATß in osteosarcoma cell lines is analyzed by using semi-quantitative PCR and immunohistochemical staining. Adenovirus-mediated overexpression of LPAATß and silencing LPAATß expression is employed to determine the effect of LPAATß on osteosarcoma cell proliferation and migration in vitro and osteosarcoma tumor growth in vivo. We have found that expression of LPAATß is readily detected in 8 of the 10 analyzed human osteosarcoma lines. Exogenous expression of LPAATß promotes osteosarcoma cell proliferation and migration, while silencing LPAATß expression inhibits these cellular characteristics. We further demonstrate that exogenous expression of LPAATß effectively promotes tumor growth, while knockdown of LPAATß expression inhibits tumor growth in an orthotopic xenograft model of human osteosarcoma. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest that LPAATß expression may be associated with the aggressive phenotypes of human osteosarcoma and that LPAATß may play an important role in regulating osteosarcoma cell proliferation and tumor growth. Thus, targeting LPAATß 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.