Open Access

Three-dimensional hydrogel is suitable for targeted investigation of amoeboid migration of glioma cells

  • Authors:
    • Yubao Huang
    • Luqing Tong
    • Li Yi
    • Chen Zhang
    • Long Hai
    • Tao Li
    • Shengping Yu
    • Wei Wang
    • Zhennan Tao
    • Haiwen Ma
    • Peidong Liu
    • Yang Xie
    • Xuejun Yang
  • View Affiliations

  • Published online on: October 26, 2017     https://doi.org/10.3892/mmr.2017.7888
  • Pages:250-256
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioblastoma (GBM) invasion and migration are key biological behaviors leading to refractoriness to current therapies and infiltration into the non‑tumor brain parenchyma. GBM cell migration is strongly dependent on tumor architecture in vivo, which is absent in traditional two‑dimensional (2D) monolayer culture. The present study applied a three‑dimensional (3D) hydrogel model to rebuild the tumor architecture in vitro. Treatment with NSC23766, a specific inhibitor of Ras‑related C3 botulinum toxin substrate 1 (Rac1), inhibited the mesenchymal invasiveness however triggered the amoeboid motility called mesenchymal‑amoeboid transition (MAT). Notably, NSC23766 stimulated U87 GBM cell migration in the 3D hydrogel. However, this compound inhibited cell motility in 2D monolayer culture without tumor architecture for MAT, suggesting the advantage of 3D hydrogel to investigate tumor cell invasion. Due to the inverse interaction of Rac1 and Ras homolog family member A (RhoA) signaling in the transition between mesenchymal and amoeboid morphology, simultaneous treatment of NSC23766 and Y27632 (selective Rho associated coiled‑coil containing protein kinase 1 inhibitor), abolished U87 GBM cell migration through inhibiting MAT and amoeboid‑mesenchymal transition. In addition, Y27632 induced integrin expression which gave rise to the focal adhesion to facilitate the mesenchymal invasion. The results of the present study demonstrated that the 3D hydrogel was a preferable model in vitro to study tumor cell invasion and migration. The combined inhibition of Rac1 and RhoA signaling would be a promising strategy to suppress GBM invasion.

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January 2018
Volume 17 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
Ranked #19/128 Medicine Research and Experimental
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APA
Huang, Y., Tong, L., Yi, L., Zhang, C., Hai, L., Li, T. ... Yang, X. (2018). Three-dimensional hydrogel is suitable for targeted investigation of amoeboid migration of glioma cells. Molecular Medicine Reports, 17, 250-256. https://doi.org/10.3892/mmr.2017.7888
MLA
Huang, Y., Tong, L., Yi, L., Zhang, C., Hai, L., Li, T., Yu, S., Wang, W., Tao, Z., Ma, H., Liu, P., Xie, Y., Yang, X."Three-dimensional hydrogel is suitable for targeted investigation of amoeboid migration of glioma cells". Molecular Medicine Reports 17.1 (2018): 250-256.
Chicago
Huang, Y., Tong, L., Yi, L., Zhang, C., Hai, L., Li, T., Yu, S., Wang, W., Tao, Z., Ma, H., Liu, P., Xie, Y., Yang, X."Three-dimensional hydrogel is suitable for targeted investigation of amoeboid migration of glioma cells". Molecular Medicine Reports 17, no. 1 (2018): 250-256. https://doi.org/10.3892/mmr.2017.7888