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Glial cell line-derived neurotrophic factor promotes invasive behaviour in testicular seminoma cells.
MedLine Citation:
PMID:  22519471     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The glial cell line-derived neurotrophic factor (GDNF) has multiple functions that promote cell survival, proliferation and migration in different cell types. The experimental over-expression of GDNF in mouse testis leads to infertility and promotes seminomatous germ cell tumours in older animals, which suggests that deregulation of the GDNF pathway may be implicated in germ cell carcinogenesis. GDNF activates downstream pathways upon binding to its specific co-receptor GDNF family receptor-a 1 (GFRA1). This complex then interacts with Ret and other co-receptors to activate several intracellular signalling cascades. To explore the involvement of the GDNF pathway in the onset and progression of testicular germ cell tumours, we analysed GFRA1 and Ret expression patterns in seminoma samples. We demonstrated, via immunohistochemistry, that GFRA1, but not Ret, is over-expressed in in situ carcinoma (CIS) and in intratubular and invasive seminoma cells compared with normal human germ cells. Functional analysis of the GDNF biological activity was performed on TCam-2 seminoma cell line. Reverse transcription-PCR (RT-PCR) and immunohistochemical analyses demonstrate that TCam-2 cells express both GFRA1 and Ret mRNA, but only GFRA1 was detected at the protein level. In TCam-2 cells, although GDNF is not mitogenic, it is able to induce migration, as demonstrated by a Boyden chamber assay, possibly through the Src and MEK pathways. Moreover, GDNF promotes invasive behaviour, an effect dependent on pericellular protease activity, possibly through the activity of matrix metalloproteinases. GFRA1 over-expression in CIS and seminoma cells, along with the functional analyses in TCam-2 cells, suggests an involvement of the GDNF pathway in the progression of testicular germ cell cancer.
Authors:
F Ferranti; B Muciaccia; G Ricci; L Dovere; R Canipari; F Magliocca; M Stefanini; A Catizone; E Vicini
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-23
Journal Detail:
Title:  International journal of andrology     Volume:  -     ISSN:  1365-2605     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8000141     Medline TA:  Int J Androl     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.
Affiliation:
Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Section of Histology, Fondazione Pasteur Cenci Bolognetti, Sapienza University of Rome, Rome Department of Experimental Medicine, Second University of Naples, Naples Department of Radiological, Oncologic and Pathologic Sciences, Sapienza University of Rome, Rome, Italy.
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