Proteomic profiling of cisplatin-resistant and cisplatin-sensitive germ cell tumor cell lines using quantitative mass spectrometry

ABSTRACT: Testicular germ cell tumors (GCTs) are the most common malignant solid neoplasms in men between the age of 15 and 40 with an increasing incidence seen over the last four decades. Histologically, type II GCT are divided into seminomas (SEM) and non-seminomatous GCT (NSGCT) according to the WHO. NSGCT comprise distinct subentities, e.g. embry-onal carcinomas (EC), yolk sac tumors, choriocarcinomas and teratomas (TER). The distinction between SEM and NSGCT is important because of varying treatment approaches, treatment responses and patients’ prognosis. The treatment of GCTs primarily comprises a radical inguinal orchiectomy of the affected testis. Subsequent cisplatin-based combination chemotherapy is required in metastatic GCTs. The introduction of cisplatin-based com-bination chemotherapy has led to cure rates of up to 90% even in metastatic disease stages. Teratomas are of particular interest, as they are uniformly cisplatin-resistant and sur-gery is the only successful therapy. The number of patients with recurring disease that finally fail several lines of platinum-based chemotherapy is about 3-5% of all GCT patients and about 15% of patients with primary metastatic disease, but they have an exceptionally poor prognosis with a life-expectancy of only a few months. In this study, we compared cisplatin-resistant and cisplatin-sensitive cell lineages of pluripotent NTERA-2 and NCCIT as well as the nullipotent 2102EP cells (with NCCIT deriving from a TP53 mutated mixed mediastinal GCT) by high-resolution mass spectrometric analy-sis (MS) combined with stable isotope labelling with amino acids in cell culture (SILAC). The NTERA-2 and NCCIT cell lines represent EC, which can develop in all other types of NSGCT. Both cell lines represent a very well-studied in vitro model for NSGCTs.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Testis, Male Germ Cell

DISEASE(S): Testicular Germ Cell Cancer

SUBMITTER: Christof Lenz  

LAB HEAD: Christof Lenz

PROVIDER: PXD030251 | Pride | 2022-04-01

REPOSITORIES: Pride