{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:57:28Z","timestamp":1768874248435,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,23]],"date-time":"2012-04-23T00:00:00Z","timestamp":1335139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J of Andrology"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The glial cell line\u2013derived neurotrophic factor (GDNF) has multiple functions that promote cell survival, proliferation and migration in different cell types. The experimental over\u2010expression 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\u2010receptor GDNF family receptor\u2010a 1 (GFRA1). This complex then interacts with Ret and other co\u2010receptors 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\u2010expressed 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\u20102 seminoma cell line. Reverse transcription\u2010PCR (RT\u2010PCR) and immunohistochemical analyses demonstrate that TCam\u20102 cells express both GFRA1 and Ret mRNA, but only GFRA1 was detected at the protein level. In TCam\u20102 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\u2010expression in CIS and seminoma cells, along with the functional analyses in TCam\u20102 cells, suggests an involvement of the GDNF pathway in the progression of testicular germ cell cancer.<\/jats:p>","DOI":"10.1111\/j.1365-2605.2012.01267.x","type":"journal-article","created":{"date-parts":[[2012,4,23]],"date-time":"2012-04-23T10:26:05Z","timestamp":1335176765000},"page":"758-768","source":"Crossref","is-referenced-by-count":15,"title":["Glial cell line\u2013derived neurotrophic factor promotes invasive behaviour in testicular seminoma cells"],"prefix":"10.1111","volume":"35","author":[{"given":"F.","family":"Ferranti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Muciaccia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Ricci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Dovere","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Canipari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Magliocca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Stefanini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Catizone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Vicini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,4,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn812"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.05.010"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/373339a0"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209582"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.109.007658"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2009.01043.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067100"},{"key":"e_1_2_7_9_1","first-page":"173","article-title":"Glial cell line\u2010derived neurotrophic factor (GDNF) and its receptors GFRalpha\u20101 and GFRalpha\u20102 in the human testis","volume":"106","author":"Davidoff MS","year":"2001","journal-title":"Ital J Anat Embryol"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.7.519"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-007-0527-y"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-2343"},{"key":"e_1_2_7_13_1","unstructured":"FerlayJ ShinHR BrayF FormanD MathersC&ParkinDM. 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