Skip to Main content Skip to Navigation
Journal articles

Glial cell line-derived neurotrophic factor promotes invasive behaviour in testicular seminoma cells.

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [57 references]  Display  Hide  Download

https://hal-riip.archives-ouvertes.fr/pasteur-00957431
Contributor : Istituto Pasteur Fondazione Cenci Bolognetti <>
Submitted on : Monday, March 10, 2014 - 2:03:56 PM
Last modification on : Monday, February 18, 2019 - 2:03:04 PM
Long-term archiving on: : Sunday, April 9, 2017 - 10:24:18 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

F. Ferranti, B. Muciaccia, G. Ricci, L. Dovere, R. Canipari, et al.. Glial cell line-derived neurotrophic factor promotes invasive behaviour in testicular seminoma cells.. International Journal of Andrology, Wiley, 2012, 35 (5), pp.758-68. ⟨10.1111/j.1365-2605.2012.01267.x⟩. ⟨pasteur-00957431⟩

Share

Metrics

Record views

136