Functional expression of olfactory receptors in human primary melanoma and melanoma metastasis

Exp Dermatol. 2017 Jul;26(7):569-576. doi: 10.1111/exd.13316. Epub 2017 Apr 21.

Abstract

We identified the olfactory receptor 51E2 in human melanoma and have measured both OR51E2 mRNA and protein expression in melanoma tissue sections. qPCR analysis revealed that the receptor is upregulated in melanoma cells compared to normal melanocytes, indicating that OR51E2 may play a role in early melanoma development and progression. Activation of endogenous OR51E2 in cultured cells derived from metastatic and vertical-growth phase (VGP) by its ligand β-ionone results in an increase in the intracellular Ca2+ concentration. RNAi experiments showed that the β-ionone-induced Ca2+ signal depends on the activation of OR51E2. Furthermore, OR51E2 activation inhibits the growth of VGP melanoma cells via apoptotic processes. Cell motility assays revealed that treatment with β-ionone decreases the migration of VGP melanoma cells. Overall, our data demonstrates that OR51E2 is involved in the regulation of cell proliferation and migration, suggesting that it may serve as a novel target for melanoma therapy.

Keywords: G protein-coupled receptors; cancer; cell migration; cell proliferation; ectopic expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Ligands
  • Melanocytes / metabolism
  • Melanoma / metabolism*
  • Neoplasm Metastasis
  • Neoplasm Proteins / metabolism*
  • Norisoprenoids / chemistry
  • Polymerase Chain Reaction
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptors, Odorant / metabolism*
  • Signal Transduction
  • Skin Neoplasms / metabolism*
  • Treatment Outcome

Substances

  • Ligands
  • Neoplasm Proteins
  • Norisoprenoids
  • OR51E2 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, Odorant
  • beta-ionone
  • Calcium