Abstract
BackgroundMetabolic reprogramming is one of the hallmarks of cancer. The hyperglycolytic phenotype is often associated with the overexpression of metabolism-associated proteins, such as monocarboxylate transporters (MCTs). MCTs are little explored in germ cell tumors (GCTs), thus, the opportunity to understand the relevance of these metabolic markers and their chaperone CD147 in this type of tumor arises. The main aim of this study was to evaluate the expression of MCT1, MCT2, MCT4 and CD147 in testicular GCT samples and the clinicopathological significance of these metabolism related proteins.ResultsMCT1, MCT4 and CD147 were associated with higher stages, higher M and N stages and histological type, while MCT4 was also associated with higher risk stratification, presence of vascular invasion, and lower overall and event free survival. MCT4 silencing in JEG-3 had no significant effect in cell viability, proliferation and death, as well as extracellular levels of glucose and lactate. However, MCT4-silenced cells showed an increase in migration and invasion.ConclusionThe proteins herein studied, with the exception of MCT2, were associated with characteristics of worse prognosis, lower global and event free survival of patients with GCTs. Also, in vitro MCT4 silencing stimulated cell migration and invasion.Materials and MethodsImmunohistochemical expression was evaluated on samples from 149 adult patients with testicular GCT, arranged in Tissue Microarrays (TMAs), and associated with the clinicopathological data. Also, MCT4 silencing studies using siRNA were performed in JEG-3 cells.
Highlights
Testicular germ cell tumors (TGCTs) are relatively rare neoplasms, they are the most frequent solid tumors affecting young males [1, 2]
MCT1, MCT4 and CD147 were associated with higher stages, higher M and N stages and histological type, while MCT4 was associated with higher risk stratification, presence of vascular invasion, and lower overall and event free survival
MCT4 silencing in JEG-3 had no significant effect in cell viability, proliferation and death, as well as extracellular levels of glucose and lactate
Summary
Testicular germ cell tumors (TGCTs) are relatively rare neoplasms, they are the most frequent solid tumors affecting young males [1, 2]. The precise functional mechanisms involving isochromosome 12p as a player in TGCTs are yet to be described (reviewed in [5]) Despite this lack of information, other relevant biological characteristics involved in the multistep development of human tumors, as proposed by Hanahan and Weinberg [6], should be considered in the pursuit to a better understanding of the biological features of TGCTs. Despite this lack of information, other relevant biological characteristics involved in the multistep development of human tumors, as proposed by Hanahan and Weinberg [6], should be considered in the pursuit to a better understanding of the biological features of TGCTs In this context, the reprogramming of energy metabolism, recently described as one of the hallmarks of cancer cells [6, 7], emerges as a promising candidate. The main aim of this study was to evaluate the expression of MCT1, MCT2, MCT4 and CD147 in testicular GCT samples and the clinicopathological significance of these metabolism related proteins
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