Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo 14784400, Brazil.
Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo 14784400, Brazil.
Mol Med Rep. 2024 Dec;30(6). doi: 10.3892/mmr.2024.13352. Epub 2024 Oct 11.
Germ cell tumors (GCTs) constitute diverse neoplasms arising in the gonads or extragonadal locations. Testicular GCTs (TGCTs) are the predominant solid tumors in adolescents and young men. Despite cisplatin serving as the primary therapeutic intervention for TGCTs, 10‑20% of patients with advanced disease demonstrate resistance to cisplatin‑based chemotherapy, and epithelial‑mesenchymal transition (EMT) is a potential contributor to this resistance. EMT is regulated by various factors, including the snail family transcriptional repressor 2 () transcriptional factor, and, to the best of our knowledge, remains unexplored within TGCTs. Therefore, the present study investigated the EMT transcription factor in TGCTs. analyses were performed to investigate the expression of EMT markers in TGCTs. In addition, a cisplatin‑resistant model for TGCTs was developed using the NTERA‑2 cell line, and a mouse model was also established. Subsequently, EMT was assessed both and within the cisplatin‑resistant models using quantitative PCR and western blot analyses. The results of the analysis showed that the different histologies exhibited distinct expression profiles for EMT markers. Seminomas exhibited a lower expression of EMT markers, whereas embryonal carcinomas and mixed GCT demonstrated high expression. Notably, patients with lower expression had longer median progression‑free survival (46.4 months vs. 28.0 months, P=0.022). In the analysis, EMT‑associated genes [fibronectin; vimentin (); actin, α2, smooth muscle; collagen type I α1; transforming growth factor‑β1; and ] were upregulated in the cisplatin‑resistant NTERA‑2 (NTERA‑2R) cell line after 72 h of cisplatin treatment. Consistent with this finding, the NTERA‑2R mouse model demonstrated a significant upregulation in the expression levels of VIM and SLUG. In conclusion, the present findings suggested that may serve a crucial role in connecting EMT with the development of cisplatin resistance, and targeting may be a putative therapeutic strategy to mitigate cisplatin resistance.
生殖细胞肿瘤（GCT）是发生在性腺或性腺外部位的多种肿瘤。睾丸生殖细胞肿瘤（TGCT）是青少年和年轻男性中主要的实体肿瘤。尽管顺铂是 TGCT 的主要治疗干预措施，但 10-20%的晚期疾病患者对顺铂为基础的化疗产生耐药性，上皮-间充质转化（EMT）是产生这种耐药性的潜在因素。EMT 受多种因素调控，包括 snail 家族转录阻遏物 2（）转录因子，据我们所知，在 TGCT 中尚未得到探索。因此，本研究探讨了 TGCT 中的 EMT 转录因子。进行了分析，以研究 EMT 标志物在 TGCT 中的表达。此外，使用 NTERA-2 细胞系建立了 TGCT 的顺铂耐药模型，并建立了小鼠模型。随后，通过定量 PCR 和 Western blot 分析评估了顺铂耐药模型中的 EMT 和。分析结果表明，不同的组织学表现出 EMT 标志物的不同表达谱。精原细胞瘤表现出 EMT 标志物的低表达，而胚胎癌和混合 GCT 则表现出高表达。值得注意的是，表达水平较低的患者中位无进展生存期更长（46.4 个月比 28.0 个月，P=0.022）。在分析中，顺铂处理 72 小时后，顺铂耐药的 NTERA-2（NTERA-2R）细胞系中 EMT 相关基因[纤连蛋白；波形蛋白（）；肌动蛋白，α2，平滑肌；I 型胶原；转化生长因子-β1；和]上调。与此一致的是，NTERA-2R 小鼠模型中 VIM 和 SLUG 的表达水平显著上调。总之，本研究结果表明，可能在 EMT 与顺铂耐药的发展之间发挥关键作用，靶向可能是减轻顺铂耐药的潜在治疗策略。
