Lysophosphatidic Acid Acyltransferase β (LPAATβ) Promotes the Tumor Growth of Human Osteosarcoma

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