The neurotrophin Neuritin1 (cpg15) is involved in melanoma migration, attachment independent growth, and vascular mimicry

Oncotarget. 2017 Jan 3;8(1):1117-1131. doi: 10.18632/oncotarget.13585.

Abstract

The neurotrophin Neuritin1 (NRN1; cpg15) belongs to the candidate plasticity gene (CPG) family and is expressed in postmitotic-differentiating neurons of the developmental nervous system and neuronal structures associated with plasticity in the brain of human adult.Our newest findings document that NRN1 deregulation could contribute also to disease development and have impact on malignant melanoma. Our analyses displayed the over-expression of NRN1 in melanoma in vitro and in vivo, shown by immunohistochemistry and qRT-PCR on microdissected melanoma tissue; furthermore, soluble NRN1 was detectable in tissue culture supernatant and serum of melanoma patients.To investigate the role of NRN1 in melanoma we performed knockdown, over-expression and recombinant-NRN1-treatment experiments affiliated by functional assays. Our results show that migration, attachment independent growth and vasculogenesis were affected after manipulation of NRN1 on endogenous and extrinsic level. Interestingly, high NRN1 serum levels correlate with low MIA serum levels (< 10ng/ml). Therefore, we speculate that NRN1 could be a marker for early melanoma stages, in particular.In summary, we detected an overexpression of NRN1 in melanoma patient. In functional cell culture experiments we found a correlation between NRN1 expression and the cancerous behavior of melanoma cells.

Keywords: NRN1; biomarker; melanoma; migration; serum.

MeSH terms

  • Cell Movement / genetics
  • Cell Proliferation
  • Cells, Cultured
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • GPI-Linked Proteins / pharmacology
  • Gene Expression
  • Humans
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Melanocytes / metabolism
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / metabolism
  • Neuropeptides / genetics*
  • Neuropeptides / metabolism
  • Neuropeptides / pharmacology
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • GPI-Linked Proteins
  • NRN1 protein, human
  • Neuropeptides
  • Recombinant Proteins