Teratoma Growth Retardation by HDACi Treatment of the Tumor Embryonal Source

Abstract

Among testicular germ cell tumors, teratomas may often be very aggressive and therapy-resistant. Our aim was to investigate the impact of histone deacetylase inhibitors (HDACi) on the in vitro growth of experimental mouse teratoma by treating their embryonic source, the embryo-proper, composed only of the three germ layers. The growth of teratomas was measured for seven days, and histopathological analysis, IHC/morphometry quantification, gene enrichment analysis, and qPCR analysis on a selected panel of pluripotency and early differentiation genes followed. For the first time, within teratomas, we histopathologically assessed the undifferentiated component containing cancer stem cell-like cells (CSCLCs) and differentiated components containing numerous lymphocytes. Mitotic indices were higher than apoptotic indices in both components. Both HDACi treatments of the embryos-proper significantly reduced teratoma growth, although this could be related neither to apoptosis nor proliferation. Trichostatin A increased the amount of CSCLCs, and upregulated the mRNA expression of pluripotency/stemness genes as well as differentiation genes, e.g., T and Eomes. Valproate decreased the amount of CSCLCs, and downregulated the expressions of pluripotency/stemness and differentiation genes. In conclusion, both HDACi treatments diminished the inherent tumorigenic growth potential of the tumor embryonal source, although Trichostatin A did not diminish the potentially dangerous expression of cancer-related genes and the amount of CSCLC.

The utility of cfDNA in TGCT patient management: a systematic review

“…Testicular germ cell tumors (TGCTs) make up around 95% of all testicular tumor cases and are the most common malignancy diagnosed in men (between 15 and 44 years of age), primarily of European descent. 1 , 2 The incidence of TGCT has been steadily rising over the last 20 years 3 , 4 with the highest predicted rise in East and South European countries. 5 There have been more than 71,000 cases of testicular cancer diagnosed in 2018 alone, of which over one-third were in Europe.…”

“… 5 There have been more than 71,000 cases of testicular cancer diagnosed in 2018 alone, of which over one-third were in Europe. 1 Reasons for this rising incidence are not fully understood but are hypothesized to be a combination of inherited and epigenetic factors. 3 , 6 The initial cure rate in TGCT patients is over 95% after the standard procedure of orchiectomy and, when indicated, cisplatin-based chemotherapy treatment.…”

“… 3 , 6 The initial cure rate in TGCT patients is over 95% after the standard procedure of orchiectomy and, when indicated, cisplatin-based chemotherapy treatment. 1 , 4 , 6 However, 30% of cases will persist and 42% will recur after chemotherapy mainly due to gain of cisplatin resistance, with 50% of them dying from progressive disease. 3 , 7 In addition, reports of long-term morbidities due to the treatment are increasingly more common, with high rates of obesity, hypogonadism, erectile dysfunction, and cardiovascular disease.…”

“… 8 In this review, we will focus on the type II TGCT or the GCNIS-derived TGCT, which make up more than 90% of all adult TGCT cases. 9 , 10 GCNIS-derived TGCTs are a heterogeneous group of tumors that originate from the same precursor cell, 1 , 9 and are divided into seminomas (SEs) and non-seminomas (NSEs). SE and NSE components occur in patients in around the same ratio (1:1).…”

“…However, in ~10% of cases, SE and NSE present together as mixed germ cell tumors. 1 , 4 , 9 , 11 , 12 NSEs are further subdivided into embryonal carcinomas, teratomas (TE), choriocarcinomas, and yolk sac tumors. 3 , 8 , 9 The correct diagnosis of TGCT components and their ratio is important for treatment selection.…”