Teratoma Growth Retardation by HDACi Treatment of the Tumor Embryonal Source.
Jure KrasicLucija SkaraMonika UlamecAna Katusic BojanacSanja DabelicFloriana Bulic-JakusDavor JezekNino SincicPublished in: Cancers (2020)
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.
Keyphrases
- histone deacetylase
- genome wide
- germ cell
- genome wide identification
- cancer stem cells
- stem cells
- cell death
- oxidative stress
- poor prognosis
- epithelial mesenchymal transition
- signaling pathway
- squamous cell carcinoma
- papillary thyroid
- pregnant women
- long non coding rna
- endoplasmic reticulum stress
- climate change
- cell cycle
- cell fate
- lymph node metastasis
- bone marrow