The neurotrophin neuritin1 (cpg15) is involved in melanoma migration, attachment independent growth, and vascular mimicry

Abstract

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