title: 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.
  
  
  RESULTS
  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
  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.affiliation: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois, United States of America.
authors.forename: Farbod
authors.initials: F
authors.lastname: Rastegar
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Gao
authors.forename: Deana
authors.initials: D
authors.lastname: Shenaq
authors.forename: Qing
authors.initials: Q
authors.lastname: Luo
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Kim
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Eric R
authors.initials: ER
authors.lastname: Wagner
authors.forename: Enyi
authors.initials: E
authors.lastname: Huang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Gao
authors.forename: Jikun
authors.initials: J
authors.lastname: Shen
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.forename: Bai-Cheng
authors.initials: BC
authors.lastname: He
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Zuo
authors.forename: Jinyong
authors.initials: J
authors.lastname: Luo
authors.forename: Xiaoji
authors.initials: X
authors.lastname: Luo
authors.forename: Yang
authors.initials: Y
authors.lastname: Bi
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Hu
authors.forename: Linyuan
authors.initials: L
authors.lastname: Wang
authors.forename: Gaurav
authors.initials: G
authors.lastname: Luther
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D005840:Gentian Violet / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000737:chemistry; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000378:metabolism*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D008055:Lipids; D013778:Tetrazolium Salts; D013844:Thiazoles; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase; C022616:thiazolyl blue; D005840:Gentian Violet