Open Access

Epithelial‑mesenchymal transition and metastatic ability of CD133+ colorectal cancer stem‑like cells under hypoxia

  • Authors:
    • Masamichi Okada
    • Kazushige Kawai
    • Hirofumi Sonoda
    • Hiroshi Shiratori
    • Junko Kishikawa
    • Hiroshi Nagata
    • Hiroaki Nozawa
    • Kazuhito Sasaki
    • Manabu Kaneko
    • Koji Murono
    • Shigenobu Emoto
    • Yuuki Iida
    • Hiroaki Ishii
    • Yuichiro Yokoyama
    • Hiroyuki Anzai
    • Kiyoshi Hasegawa
    • Soichiro Ishihara
  • View Affiliations

  • Published online on: November 9, 2020     https://doi.org/10.3892/ol.2020.12280
  • Article Number: 19
  • Copyright: © Okada et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although CD133 is a representative cancer stem cell marker, its function in tumor aggressiveness under hypoxia remains unclear. Therefore, the present study aimed to investigate the associations between CD133, the epithelial‑mesenchymal transition and distant metastasis in colorectal cancer. CD133+ and CD133 cells were isolated from a single colorectal cancer cell line LoVo, and their adhesive and migratory properties were compared under hypoxic conditions. Immunostaining analysis was performed to determine CD133 expression in clinical samples of primary tumors, as well as liver and peritoneal metastases. Under hypoxia, the expression levels of hypoxia‑inducible factor (HIF)‑1α and the epithelial‑mesenchymal transition markers N‑cadherin and vimentin were significantly higher in the CD133+ compared with those in the CD133 cells. Furthermore, the migratory ability of the CD133+ cells was higher compared with that of the CD133 cells under hypoxia. By contrast, the expression levels of β1 integrin were significantly lower in the CD133+ cells under hypoxia compared with those in the CD133 cells. Immunohistochemical analysis of clinical samples revealed that the levels of CD133 expression in metastatic tissues from the liver were significantly higher compared with those in the corresponding primary tumors, whereas CD133 expression levels in peritoneal metastatic tissues were significantly lower compared with those in the corresponding primary tumors. In conclusion, compared with the CD133 cells, the CD133+ colorectal cancer cells exhibited enhanced levels of HIF‑1α expression and tumor cell migration during hypoxia. This was associated with an increased ability of epithelial‑mesenchymal transition, possibly leading to the acquisition of an increased hematogenous metastatic potential and eventually resulting in liver metastasis. High β1 integrin expression levels in the CD133 cells under hypoxia may serve a key role in cell adhesion to the peritoneum, resulting in peritoneal metastasis.
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January-2021
Volume 21 Issue 1

Print ISSN: 1792-1074
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Spandidos Publications style
Okada M, Kawai K, Sonoda H, Shiratori H, Kishikawa J, Nagata H, Nozawa H, Sasaki K, Kaneko M, Murono K, Murono K, et al: Epithelial‑mesenchymal transition and metastatic ability of CD133+ colorectal cancer stem‑like cells under hypoxia. Oncol Lett 21: 19, 2021
APA
Okada, M., Kawai, K., Sonoda, H., Shiratori, H., Kishikawa, J., Nagata, H. ... Ishihara, S. (2021). Epithelial‑mesenchymal transition and metastatic ability of CD133+ colorectal cancer stem‑like cells under hypoxia. Oncology Letters, 21, 19. https://doi.org/10.3892/ol.2020.12280
MLA
Okada, M., Kawai, K., Sonoda, H., Shiratori, H., Kishikawa, J., Nagata, H., Nozawa, H., Sasaki, K., Kaneko, M., Murono, K., Emoto, S., Iida, Y., Ishii, H., Yokoyama, Y., Anzai, H., Hasegawa, K., Ishihara, S."Epithelial‑mesenchymal transition and metastatic ability of CD133+ colorectal cancer stem‑like cells under hypoxia". Oncology Letters 21.1 (2021): 19.
Chicago
Okada, M., Kawai, K., Sonoda, H., Shiratori, H., Kishikawa, J., Nagata, H., Nozawa, H., Sasaki, K., Kaneko, M., Murono, K., Emoto, S., Iida, Y., Ishii, H., Yokoyama, Y., Anzai, H., Hasegawa, K., Ishihara, S."Epithelial‑mesenchymal transition and metastatic ability of CD133+ colorectal cancer stem‑like cells under hypoxia". Oncology Letters 21, no. 1 (2021): 19. https://doi.org/10.3892/ol.2020.12280