Open Access

Cisplatin‑resistant germ cell tumor models: An exploration of the epithelial‑mesenchymal transition regulator SLUG

  • Authors:
    • Ingridy Izabella Vieira Cardoso
    • Marcela Nunes Rosa
    • Daniel Antunes Moreno
    • Letícia Maria Barbosa Tufi
    • Lorrayne Pereira Ramos
    • Larissa Alessandra Bourdeth Pereira
    • Lenilson Silva
    • Janaina Mello Soares Galvão
    • Isabela Cristiane Tosi
    • André Van Helvoort Lengert
    • Marcelo Cavalcanti Da Cruz
    • Silvia Aparecida Teixeira
    • Rui Manuel Reis
    • Luiz Fernando Lopes
    • Mariana Tomazini Pinto
  • View Affiliations

  • Published online on: October 4, 2024     https://doi.org/10.3892/mmr.2024.13352
  • Article Number: 228
  • Copyright: © Vieira Cardoso et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 (SLUG) transcriptional factor, and, to the best of our knowledge, remains unexplored within TGCTs. Therefore, the present study investigated the EMT transcription factor SLUG in TGCTs. In silico 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 in vitro and in vivo within the cisplatin‑resistant models using quantitative PCR and western blot analyses. The results of the in silico 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 SLUG expression had longer median progression‑free survival (46.4 months vs. 28.0 months, P=0.022). In the in vitro analysis, EMT‑associated genes [fibronectin; vimentin (VIM); actin, α2, smooth muscle; collagen type I α1; transforming growth factor‑β1; and SLUG] 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 SLUG may serve a crucial role in connecting EMT with the development of cisplatin resistance, and targeting SLUG may be a putative therapeutic strategy to mitigate cisplatin resistance.
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December-2024
Volume 30 Issue 6

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Spandidos Publications style
Vieira Cardoso II, Nunes Rosa M, Antunes Moreno D, Barbosa Tufi LM, Pereira Ramos L, Bourdeth Pereira LA, Silva L, Soares Galvão JM, Tosi IC, Van Helvoort Lengert A, Van Helvoort Lengert A, et al: Cisplatin‑resistant germ cell tumor models: An exploration of the epithelial‑mesenchymal transition regulator <em>SLUG</em>. Mol Med Rep 30: 228, 2024.
APA
Vieira Cardoso, I.I., Nunes Rosa, M., Antunes Moreno, D., Barbosa Tufi, L.M., Pereira Ramos, L., Bourdeth Pereira, L.A. ... Tomazini Pinto, M. (2024). Cisplatin‑resistant germ cell tumor models: An exploration of the epithelial‑mesenchymal transition regulator <em>SLUG</em>. Molecular Medicine Reports, 30, 228. https://doi.org/10.3892/mmr.2024.13352
MLA
Vieira Cardoso, I. I., Nunes Rosa, M., Antunes Moreno, D., Barbosa Tufi, L. M., Pereira Ramos, L., Bourdeth Pereira, L. A., Silva, L., Soares Galvão, J. M., Tosi, I. C., Van Helvoort Lengert, A., Cavalcanti Da Cruz, M., Teixeira, S. A., Reis, R. M., Lopes, L. F., Tomazini Pinto, M."Cisplatin‑resistant germ cell tumor models: An exploration of the epithelial‑mesenchymal transition regulator <em>SLUG</em>". Molecular Medicine Reports 30.6 (2024): 228.
Chicago
Vieira Cardoso, I. I., Nunes Rosa, M., Antunes Moreno, D., Barbosa Tufi, L. M., Pereira Ramos, L., Bourdeth Pereira, L. A., Silva, L., Soares Galvão, J. M., Tosi, I. C., Van Helvoort Lengert, A., Cavalcanti Da Cruz, M., Teixeira, S. A., Reis, R. M., Lopes, L. F., Tomazini Pinto, M."Cisplatin‑resistant germ cell tumor models: An exploration of the epithelial‑mesenchymal transition regulator <em>SLUG</em>". Molecular Medicine Reports 30, no. 6 (2024): 228. https://doi.org/10.3892/mmr.2024.13352