title: LPA Increases Tumor Growth and Bone Destruction Through Enhancement of Osteoclastogenic Cytokines.
abstract: BACKGROUND
  Lysophosphatidic acid (LPA) production in osteoblasts has multiple effects on osteoclast formation and function and raises the possibility that LPA may serve as a signaling molecule for the reciprocal conversation of both osteoblasts and osteoclasts within the tumor-bone microenvironment for bone resorption. However, little is known on the effect of LPA in regulating the function of both cancer cells and osteoclasts in the bone microenvironment.
  
  
  METHODS
  PC-3 tumor growth and bone destruction upon LPA administration were observed in a mouse calvarium xenograft. The osteoclastogenic cytokines produced by LPA-stimulated prostate cancer cells were also defined.
  
  
  RESULTS
  LPA administration was found to increase PC-3 tumor growth and bone destruction in a mouse calvarium xenograft. Using a cytokine antibody array, LPA highly stimulated the expression and release of osteoclastogenic cytokines from PC-3 cells. Conditioned medium from LPA-stimulated PC-3 cells containing enhanced levels of osteoclastogenic cytokines facilitated osteoclast formation. Histopathologically, LPA administration supports the erosive type of bone destruction by PC-3 prostate cancer cells.
  
  
  CONCLUSIONS
  LPA is a critical regulator in the tumor-bone microenvironment and may be a therapeutic target for patients with prostate cancer. In addition, LPA-enhanced osteoclastogenic cytokines are critical to therapeutic strategies targeting osteolytic prostate cancer.
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, U.S.A.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lindholm
authors.affiliation: Department of Dental Hygiene, College of Health Science, Eulji University, Soojung-Gu, Seongnam, Republic of Korea kiteys@eulji.ac.kr.
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Hwang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D019899:Paracrine Communication; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D012886:Skull / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012888:Skull Neoplasms / Q000378:metabolism* / Q000556:secondary*; D047368:Tumor Burden / Q000187:drug effects; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D008246:Lysophospholipids; C032881:lysophosphatidic acid
keywords: bone resorption; calvarium; cytokine; lysophosphatidic acid; osteoclast