Research Papers:

This article has been corrected. Correction in: Oncotarget. 2018; 9:36049.

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 Bizzarri, Renato Franco, J. Wolter Oosterhuis, Hans Stoop, Leendert H.J. Looijenga, Giulia Ricci _ and Angela Catizone

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Oncotarget. 2018; 9:31842-31860. https://doi.org/10.18632/oncotarget.25867

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Katia Corano Scheri1, Erica Leonetti1, Luigi Laino2, Vincenzo Gigantino3, Luisa Gesualdi1, Paola Grammatico2, Mariano Bizzarri4, Renato Franco5, J. Wolter Oosterhuis6, Hans Stoop6, Leendert H.J. Looijenga6, Giulia Ricci7,* and Angela Catizone1,*

1Department of Anatomy, Histology, Forensic-Medicine and Orthopaedics, “Sapienza” University of Rome, Italy

2Department of Molecular Medicine, Laboratory of Medical Genetics, “Sapienza” University of Rome, San Camillo-Forlanini Hospital, Rome, Italy

3Pathology Unit, Istituto Nazionale Tumori I.R.C.C.S. "Fondazione Pascale", Naples, Italy

4Department of Experimental Medicine, Systems Biology Group Lab, “Sapienza” University of Rome, Italy

5Pathological Anatomy Unit, Department of Psychic and Physic health and preventive medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy

6Department of Pathology, Laboratory for Experimental Patho-Oncology, Erasmus MC University Medical Center, Cancer Institute, Rotterdam, The Netherlands

7Department of Experimental Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy

*These authors contributed equally to this work

Correspondence to:

Giulia Ricci, email: [email protected]

Leendert H. J. Looijenga, email: [email protected]

Keywords: TGCTs; c-MET; HGF; c-MET inhibitors; cancer therapy

Received: November 06, 2017     Accepted: July 18, 2018     Published: August 07, 2018


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.

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