Open Access

VEGF‑mediated tumour growth and EMT in 2D and 3D cell culture models of hepatocellular carcinoma

  • Authors:
    • Preety Rawal
    • Dinesh Mani Tripathi
    • Vikrant Nain
    • Savneet Kaur
  • View Affiliations

  • Published online on: July 15, 2022     https://doi.org/10.3892/ol.2022.13435
  • Article Number: 315
  • Copyright: © Rawal et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The purpose of the present study was to evaluate the effects of vascular endothelial growth factor (VEGF) on tumorigenic properties in two‑dimensional (2D) and three‑dimensional (3D) cultures of hepatoma cells. The proliferation and invasion of hepatoma cells was assessed using wound healing, chemotaxis Transwell, invasion, tube‑forming and hanging drop assays in both 2D and 3D cultures. The expression levels of epithelial‑mesenchymal transition (EMT) and stemness markers were analysed using reverse transcription‑quantitative PCR (RT‑qPCR) for mRNA expression and immunofluorescence assay for protein expression. To validate the role of VEGF in tumour growth, a VEGF receptor (VEGFR) inhibitor (sorafenib) was used. The results demonstrated that the hepatoma cells formed 3D spheroids that differed in size and density in the absence and presence of the growth factor, VEGF. In all spheroids, invasion and angiogenesis were more aggressive in 3D cultures in comparison to 2D conditions following treatment with VEGF. Mechanistically, the VEGF‑mediated increase in the levels of EMT markers, including Vimentin, N‑cadherin 2 (Cadherin 2) and Thy‑1 Cell Surface Antigen was observed in the 2D and 3D cultures. Sorafenib treatment for 24 h culminated in a marked reduction in cell migration, cell‑cell adhesion, spheroid compaction and EMT gene expression in 3D models as compared to the 2D models. On the whole, the findings of the present study suggested that as compared to the 2D cell cultures, 3D cell cultures model may be used as a more realistic model for the study of tumour growth and invasion in the presence of angiogenic factors, as well as for tumour inhibitor screening.
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September-2022
Volume 24 Issue 3

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Spandidos Publications style
Rawal P, Tripathi DM, Nain V and Kaur S: VEGF‑mediated tumour growth and EMT in 2D and 3D cell culture models of hepatocellular carcinoma. Oncol Lett 24: 315, 2022
APA
Rawal, P., Tripathi, D.M., Nain, V., & Kaur, S. (2022). VEGF‑mediated tumour growth and EMT in 2D and 3D cell culture models of hepatocellular carcinoma. Oncology Letters, 24, 315. https://doi.org/10.3892/ol.2022.13435
MLA
Rawal, P., Tripathi, D. M., Nain, V., Kaur, S."VEGF‑mediated tumour growth and EMT in 2D and 3D cell culture models of hepatocellular carcinoma". Oncology Letters 24.3 (2022): 315.
Chicago
Rawal, P., Tripathi, D. M., Nain, V., Kaur, S."VEGF‑mediated tumour growth and EMT in 2D and 3D cell culture models of hepatocellular carcinoma". Oncology Letters 24, no. 3 (2022): 315. https://doi.org/10.3892/ol.2022.13435