Role of Phosphodiesterase2A in Proliferation and Migration of Human Osteosarcoma Cells

Anticancer Res. 2019 Nov;39(11):6057-6062. doi: 10.21873/anticanres.13812.

Abstract

Background/aim: The prognosis of patients with osteosarcoma is poor; therefore, new treatment strategies are urgently needed. Phosphodiesterase 2 (PDE2) is one of the 11 families (PDE1-PDE11) of the phosphodiesterase superfamily that regulates the intracellular concentrations and effects of cAMP and cGMP. This in vitro study was performed to investigate the role of PDE2 in human oral osteosarcoma HOSM-1 cells.

Materials and methods: PDE2 expression was measured by a cAMP-PDE assay and real-time-PCR. The effects of the PDE2-specific inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), 8-bromo-cAMP, and 8-bromo-cGMP on cell proliferation and migration were assessed.

Results: PDE2 activity and PDE2A mRNA expression were detected in HOSM-1 cells. Cell proliferation was inhibited by EHNA and 8-bromo-cAMP but not by 8-bromo-cGMP. Cell migration was stimulated by EHNA and 8-bromo-cGMP, but it was inhibited by 8-bromo-cAMP.

Conclusion: Cell proliferation is regulated by PDE2-cAMP signaling and cell migration is regulated by PDE2-cGMP signaling in HOSM-1 cells.

Keywords: Phosphodiesterase; migration; osteosarcoma; phosphodiesterase2A; proliferation.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Apoptosis
  • Benzyl Compounds / pharmacology
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / enzymology
  • Bone Neoplasms / pathology*
  • Cell Cycle
  • Cell Movement*
  • Cell Proliferation*
  • Cyclic AMP / pharmacology
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / pharmacology
  • Cyclic Nucleotide Phosphodiesterases, Type 2 / antagonists & inhibitors
  • Cyclic Nucleotide Phosphodiesterases, Type 2 / genetics
  • Cyclic Nucleotide Phosphodiesterases, Type 2 / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / enzymology
  • Mouth Neoplasms / pathology*
  • Osteosarcoma / drug therapy
  • Osteosarcoma / enzymology
  • Osteosarcoma / pathology*
  • Signal Transduction
  • Tumor Cells, Cultured

Substances

  • Benzyl Compounds
  • erythro-(3-nonyl-p-aminobenzyl-adenine)
  • 8-bromocyclic GMP
  • Cyclic AMP
  • Cyclic Nucleotide Phosphodiesterases, Type 2
  • PDE2A protein, human
  • Cyclic GMP
  • Adenine