c-MET receptor as potential biomarker and target molecule for malignant testicular germ cell tumors

Katia Corano Scheri, Erica Leonetti, Luigi Laino, Vincenzo Gigantino, Luisa Gesualdi, Paola Grammatico, Mariano Bizzari, Renato Franco, J Wolter Oosterhuis, Hans Stoop, Leendert H J Looijenga, Giulia Ricci, Angela Catizone

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Samenvatting

Type II testicular germ cell tumors (TGCTs) represent the most frequent malignancy in Caucasian males (20-40 years). Even if diagnosed with disseminated disease, >80% of patients are cured; however, a small percentage of cases progress and result in death. It is commonly accepted that these cancers arise from a disturbed testicular embryonic niche that leads to the block of gonocyte differentiation. The subsequent development of the invasive seminomas and non-seminomas is due to a combination of genetic, epigenetic and microenvironment-based alterations (genvironment). Hepatocyte growth factor (HGF) is present in the testicular microenvironment, together with its receptor c-MET, from early embryonic development to an adult stage. In addition, c-MET is a well-known proto-oncogene involved in the onset and progression of various human cancers. Herein, we have investigated the expression and availability of HGF and c-MET in TCam-2, NCCIT and NT2D1 cells, which are type II (T)GCT representative cell lines, and the effect of c-MET activation/repression on the regulation of cancerous biological processes. We found that NT2D1 cells increase their proliferation, polarized migration, and invasion in response to HGF administration. NCCIT cells respond to HGF stimulation only partially, whereas TCam-2 cells do not respond to HGF, at least according to the investigated parameters. Interestingly, the immunohistochemical study of c-MET distribution in TGCTs confirm its presence in both seminoma and non-seminoma lesions with different patterns. Notably, we found the highest c-MET immunoreactivity in the epithelial elements of the various components of TGCTs: teratoma, yolk sac tumor and choriocarcinoma.

Originele taal-2Engels
Pagina's (van-tot)31842-31860
Aantal pagina's19
TijdschriftOncotarget
Volume9
Nummer van het tijdschrift61
DOI's
StatusGepubliceerd - 7 aug. 2018
Extern gepubliceerdJa

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