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

被引:23
作者
Bosserhoff, Anja Katrin [1 ]
Schneider, Nadja [1 ]
Ellmann, Lisa [2 ]
Heinzerling, Lucie [3 ]
Kuphal, Silke [1 ]
机构
[1] Univ Erlangen Nurnberg, Emil Fischer Ctr, Inst Biochem, D-91054 Erlangen, Germany
[2] Univ Regensburg, Inst Funct Gen, D-93053 Regensburg, Germany
[3] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Dermatol, D-91054 Erlangen, Germany
关键词
NRN1; melanoma; migration; biomarker; serum; ACTIVITY-REGULATED GENES; MALIGNANT-MELANOMA; METASTATIC MELANOMA; INHIBITORY-ACTIVITY; S100; PROTEIN; CELLS; EXPRESSION; CANCER; APOPTOSIS; THERAPY;
D O I
10.18632/oncotarget.13585
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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, overexpression 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.
引用
收藏
页码:1117 / 1131
页数:15
相关论文
共 40 条
[1]
PPISURV: a novel bioinformatics tool for uncovering the hidden role of specific genes in cancer survival outcome [J].
Antonov, A. V. ;
Krestyaninova, M. ;
Knight, R. A. ;
Rodchenkov, I. ;
Melino, G. ;
Barlev, N. A. .
ONCOGENE, 2014, 33 (13) :1621-1628
[2]
BioProfiling.de: analytical web portal for high-throughput cell biology [J].
Antonov, Alexey V. .
NUCLEIC ACIDS RESEARCH, 2011, 39 :W323-W327
[3]
Final Version of 2009 AJCC Melanoma Staging and Classification [J].
Balch, Charles M. ;
Gershenwald, Jeffrey E. ;
Soong, Seng-jaw ;
Thompson, John F. ;
Atkins, Michael B. ;
Byrd, David R. ;
Buzaid, Antonio C. ;
Cochran, Alistair J. ;
Coit, Daniel G. ;
Ding, Shouluan ;
Eggermont, Alexander M. ;
Flaherty, Keith T. ;
Gimotty, Phyllis A. ;
Kirkwood, John M. ;
McMasters, Kelly M. ;
Mihm, Martin C., Jr. ;
Morton, Donald L. ;
Ross, Merrick I. ;
Sober, Arthur J. ;
Sondak, Vernon K. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (36) :6199-6206
[4]
Neurotrophins in skin biology and pathology [J].
Botchkarev, Vladimir A. ;
Yaar, Mina ;
Peters, Eva M. J. ;
Raychaudhuri, Siba P. ;
Botchkareva, Natalia V. ;
Marconi, Alessandra ;
Raychaudhuri, Smriti K. ;
Paus, Ralf ;
Pincelli, Carlo .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2006, 126 (08) :1719-1727
[5]
CD271 is an imperfect marker for melanoma initiating cells [J].
Cheli, Yann ;
Bonnazi, Vanessa F. ;
Jacquel, Arnaud ;
Allegra, Maryline ;
De Donatis, Gian Marco ;
Bahadoran, Philippe ;
Bertolotto, Corine ;
Ballotti, Robert .
ONCOTARGET, 2014, 5 (14) :5272-5283
[6]
Human CD271-Positive Melanoma Stem Cells Associated with Metastasis Establish Tumor Heterogeneity and Long-term Growth [J].
Civenni, Gianluca ;
Walter, Anne ;
Kobert, Nikita ;
Mihic-Probst, Daniela ;
Zipser, Marie ;
Belloni, Benedetta ;
Seifert, Burkhardt ;
Moch, Holger ;
Dummer, Reinhard ;
van den Broek, Maries ;
Sommer, Lukas .
CANCER RESEARCH, 2011, 71 (08) :3098-3109
[7]
Distinct sets of genetic alterations in melanoma [J].
Curtin, JA ;
Fridlyand, J ;
Kageshita, T ;
Patel, HN ;
Busam, KJ ;
Kutzner, H ;
Cho, KH ;
Aiba, S ;
Bröcker, EB ;
LeBoit, PE ;
Pinkel, D ;
Bastian, BC .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (20) :2135-2147
[8]
S100-beta, melanoma-inhibiting activity, and lactate dehydrogenase discriminate progressive from nonprogressive American Joint Committee on Cancer stage IV melanoma [J].
Deichmann, M ;
Benner, A ;
Bock, M ;
Jäckel, A ;
Uhl, K ;
Waldmann, V ;
Näher, H .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (06) :1891-1896
[9]
Evaluation of multiple serum markers in advanced melanoma [J].
Diaz-Lagares, Angel ;
Alegre, Estibaliz ;
Arroyo, Ainhoa ;
Gonzalez-Cao, Maria ;
Zudaire, Maria E. ;
Viteri, Santiago ;
Martin-Algarra, Salvador ;
Gonzalez, Alvaro .
TUMOR BIOLOGY, 2011, 32 (06) :1155-1161
[10]
Djukanovic D, 2000, ANTICANCER RES, V20, P2203