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

• Type of Material: Article
• Authors: Farbod Rastegar, University of Chicago; Jian-Li Gao, University of Chicago; Deana Shenaq, University of Chicago; Qing Luo, University of Chicago; Qiong Shi, University of Chicago; Stephanie H. Kim, University of Chicago; Wei Jiang, University of Chicago; Eric Wagner, Emory University; Enyi Huang, University of Chicago; Yanhong Gao, University of Chicago; Jikun Shen, University of Chicago; Ke Yang, University of Chicago; Bai-Cheng He, University of Chicago; Liang Chen, University of Chicago; Guo-Wei Zuo, University of Chicago; Jinyong Luo, University of Chicago; Xiaoji Luo, University of Chicago; Yang Bi, University of Chicago; Xing Liu, University of Chicago; Mi Li, University of Chicago; Ning Hu, University of Chicago; Linyuan Wang, University of Chicago; Gaurav Luther, University of Chicago; Hue H Luu, University of Chicago; Rex C. Haydon, University of Chicago; Tong-Chuan He, University of Chicago
• Language: English
• Date: 2010-12-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2010 Rastegar et al.
• License: Creative Commons Attribution 2.5 Generic
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0014182
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 5
• Issue: 12
• Start Page: e14182
• End Page: e14182
• Grant/Funding Information: The reported work was supported in part by research grants from the Brinson Foundation (TCH), National Institutes of Health (TCH and HHL) and the Animal Imaging Pilot Grant from The University of Chicago Comprehensive Cancer Center (to RCH).
• Keywords: PULMONARY METASTASES; RECOMBINANT ADENOVIRUSES; MESENCHYMAL STEM-CELLS; Multidisciplinary Sciences; OSTEOGENIC DIFFERENTIATION; PHOSPHATIDIC-ACID; OSTEOBLAST DIFFERENTIATION; Science & Technology - Other Topics; Science & Technology; OVARIAN-CANCER; MOLECULAR-MECHANISMS; EXTREMITY OSTEOSARCOMA; PROGENITOR CELLS
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

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 b (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 semiquantitative 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.