LPA increases tumor growth and bone destruction through enhancement of osteoclastogenic cytokines

Paul F Lindholm, Young Sun Hwang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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. Materials and Methods: PC-3 tumor growth and bone destruction upon LPA administration were observed in a mouse calvarium xenograft. The osteoclastogenic cytokines produced by LPAstimulated 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)61-70
Number of pages10
JournalAnticancer Research
Volume36
Issue number1
StatePublished - Jan 1 2016

Keywords

  • Bone resorption
  • Calvarium
  • Cytokine
  • Lysophosphatidic acid
  • Osteoclast

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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