Open Access

Cancer‑associated fibroblasts as cellular vehicles in endometrial cancer cell migration

  • Authors:
    • Yap Chee Voon
    • Intan Sofia Omar
    • Ming-Heng Wu
    • Nur Akmarina B.M. Said
    • Ivy Chung
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  • Published online on: November 4, 2021     https://doi.org/10.3892/ol.2021.13121
  • Article Number: 3
  • Copyright: © Voon et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cell motility is a critical step in the metastasis cascade. However, the role of cancer‑associated fibroblasts (CAFs) in facilitating endometrial cancer (EC) cell motility remains unclear. The present study aimed to investigate the role of CAFs in EC motility in a 3D environment. A co‑culture model was established using an EC cell line (ECC‑1) and CAFs on a Matrigel® matrix and compared to the respective individual monocultures. It was demonstrated that endometrial CAFs increased the motility of the EC cell line, compared with the monoculture. Using live cell imaging, CAFs were observed to form cell projections that served as contact guidance for ECC‑1 cell locomotion in the spheroid formation process. These effects were specific to CAFs, as fibroblasts isolated from benign endometrial tissue samples did not form cell projections. Molecular analysis revealed that RhoA/Rho‑associated, coiled‑coil containing protein kinase 1 (ROCK1) signaling activation partly contributed to CAF‑mediated ECC‑1 cell migration. The presence of Matrigel® increased the mRNA expression of RhoA, and the mRNA and protein expression levels of its downstream effectors, ROCK1 and p‑MLC, respectively, in the ECC‑1 and CAF co‑culture, as well as the ECC‑1 and CAF monocultures. Interestingly, high phosphorylation levels of myosin light chain mediated the activation of RhoA/ROCK1 signaling in the ECC‑1 and CAF co‑culture. The ROCK1 inhibitor Y‑27632 attenuated the motility of tumor cells in ECC‑1 and CAF co‑cultures. However, similar treatment led to a significant inhibition in the motility of the CAF monoculture, but not the ECC‑1 monoculture. Moreover, tumor spheroid formation was inhibited due to a reduction in stress fiber formation in ECC‑1 and CAF co‑cultures. Altogether, these findings suggest that the regulation of the RhoA/ROCK1 signaling pathway is required for CAFs to serve as cellular vehicles in order for EC cells to migrate and form spheroids in a 3D environment.
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Spandidos Publications style
Voon YC, Omar IS, Wu M, Said NA and Chung I: Cancer‑associated fibroblasts as cellular vehicles in endometrial cancer cell migration. Oncol Lett 23: 3, 2022.
APA
Voon, Y.C., Omar, I.S., Wu, M., Said, N.A., & Chung, I. (2022). Cancer‑associated fibroblasts as cellular vehicles in endometrial cancer cell migration. Oncology Letters, 23, 3. https://doi.org/10.3892/ol.2021.13121
MLA
Voon, Y. C., Omar, I. S., Wu, M., Said, N. A., Chung, I."Cancer‑associated fibroblasts as cellular vehicles in endometrial cancer cell migration". Oncology Letters 23.1 (2022): 3.
Chicago
Voon, Y. C., Omar, I. S., Wu, M., Said, N. A., Chung, I."Cancer‑associated fibroblasts as cellular vehicles in endometrial cancer cell migration". Oncology Letters 23, no. 1 (2022): 3. https://doi.org/10.3892/ol.2021.13121