Open Access

Role of EphA2‑PI3K signaling in vasculogenic mimicry induced by cancer‑associated fibroblasts in gastric cancer cells

  • Authors:
    • Hee Sung Kim
    • You Jin Won
    • Ju Hee Shim
    • Hyun Ji Kim
    • Byung Sik Kim
    • Hea Nam Hong
  • View Affiliations

  • Published online on: July 26, 2019     https://doi.org/10.3892/ol.2019.10677
  • Pages: 3031-3038
  • Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although erythropoietin‑producing human hepatocellular receptor A2 (EphA2) signaling serves an important role in the tumor microenvironment, its contribution to vasculogenic mimicry (VM) formation in gastric cancer cells remains unclear. The aim of the present study was to investigate the role of EphA2 in VM formation induced by cancer‑associated fibroblasts (CAFs). The conditioned medium of CAFs (CAF‑CM) was prepared from 12 patients with gastric adenocarcinoma. VM was evaluated by the number of tubules and intersections in gastric cancer cells following CAF‑CM treatment. The role of EphA2‑phosphoinositide 3‑kinase (PI3K) in VM was investigated using EphA2‑targeted small interfering (si)RNAs (siEphA2), EphA2 inhibitors and PI3K‑inhibitors. CAF‑CM‑induced VM formation was significantly associated with high protein expression levels of EphA2. EphA2 inhibitor and siEphA2 manipulation significantly decreased VM formation by CAF‑CM. In siEphA2 cells, decreased expression levels of VM‑associated proteins were observed. CAF‑CM‑induced VM formation was blocked by the PI3K‑inhibitor. In conclusion, CAFs facilitate VM formation via EphA2‑PI3K signaling in gastric cancer cells. Thus, EphA2‑PI3K signaling may be required for CAF‑promoted VM formation during gastric tumorigenesis.
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September 2019
Volume 18 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Kim, H.S., Won, Y.J., Shim, J.H., Kim, H.J., Kim, B.S., & Hong, H.N. (2019). Role of EphA2‑PI3K signaling in vasculogenic mimicry induced by cancer‑associated fibroblasts in gastric cancer cells. Oncology Letters, 18, 3031-3038. https://doi.org/10.3892/ol.2019.10677
MLA
Kim, H. S., Won, Y. J., Shim, J. H., Kim, H. J., Kim, B. S., Hong, H. N."Role of EphA2‑PI3K signaling in vasculogenic mimicry induced by cancer‑associated fibroblasts in gastric cancer cells". Oncology Letters 18.3 (2019): 3031-3038.
Chicago
Kim, H. S., Won, Y. J., Shim, J. H., Kim, H. J., Kim, B. S., Hong, H. N."Role of EphA2‑PI3K signaling in vasculogenic mimicry induced by cancer‑associated fibroblasts in gastric cancer cells". Oncology Letters 18, no. 3 (2019): 3031-3038. https://doi.org/10.3892/ol.2019.10677