Clinical significance of Gremlin 1 in cervical cancer and its effects on cancer stem cell maintenance

  • Authors:
    • Masakazu Sato
    • Kei Kawana
    • Asaha Fujimoto
    • Mitsuyo Yoshida
    • Hiroe Nakamura
    • Haruka Nishida
    • Tomoko Inoue
    • Ayumi Taguchi
    • Juri Takahashi
    • Katsuyuki Adachi
    • Kazunori Nagasaka
    • Yoko Matsumoto
    • Osamu Wada‑Hiraike
    • Katsutoshi Oda
    • Yutaka Osuga
    • Tomoyuki Fujii
  • View Affiliations

  • Published online on: October 30, 2015     https://doi.org/10.3892/or.2015.4367
  • Pages: 391-397
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Abstract

Gremlin 1 is one of the bone morphogenetic protein (BMP) antagonists and is also related to differentiation in combination with BMPs and is associated with various types of diseases. Gremlin 1 is overexpressed in various types of human cancers and has been reported to play a role in cervical cancer oncogenesis. However, there is no report concerning the relationship between Gremlin 1 and cervical cancer stem cells (CSCs). The objective of the present study was to identify the clinical significance of Gremlin 1 in cervical cancer and its effects on CSC‑like properties in vitro. Clinical samples were obtained. Gremlin 1 mRNA expression levels in the cervical cancer tissues were measured by RT‑qPCR and assessed for correlation with their clinical prognosis [overall survival (OS), progression-free survival (PFS)] and with other prognostic factors. In vitro, cervical cancer, CaSki cells, exposed to Gremlin 1 (1,000 ng/ml) for 24 h were evaluated for expression of undifferentiated‑cell markers (Nanog, Oct3/4, Sox2) by RT‑qPCR, the population of ALDH‑positive cells by flow cytometry and sphere‑forming ability on a ultra‑low attachment culture dish. Cervical cancer tissues from 104 patients were collected. A high mRNA expression level of Gremlin 1 was an independent poor prognostic factor of PFS but not of OS. A high mRNA expression level of Gremlin 1 was correlated with bulky (>4 cm) tumors. The Nanog mRNA expression level was significantly increased in the CaSki cells exposed to Gremlin 1 (P=0.0008) but not Oct3/4 and Sox2 mRNA expression levels. The population of ALDH‑positive cells in the Gremlin 1‑exposed cells was 1.41‑fold higher compared with the control (P=0.0184). Sphere‑forming ability was increased when 1,000 Gremlin 1‑exposed cells were seeded (P=0.0379). In cervical cancer, it is suggested that Gremlin 1 may have a role in clinical recurrence and maintaining CSC-like properties.
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January-2016
Volume 35 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Sato M, Kawana K, Fujimoto A, Yoshida M, Nakamura H, Nishida H, Inoue T, Taguchi A, Takahashi J, Adachi K, Adachi K, et al: Clinical significance of Gremlin 1 in cervical cancer and its effects on cancer stem cell maintenance. Oncol Rep 35: 391-397, 2016
APA
Sato, M., Kawana, K., Fujimoto, A., Yoshida, M., Nakamura, H., Nishida, H. ... Fujii, T. (2016). Clinical significance of Gremlin 1 in cervical cancer and its effects on cancer stem cell maintenance. Oncology Reports, 35, 391-397. https://doi.org/10.3892/or.2015.4367
MLA
Sato, M., Kawana, K., Fujimoto, A., Yoshida, M., Nakamura, H., Nishida, H., Inoue, T., Taguchi, A., Takahashi, J., Adachi, K., Nagasaka, K., Matsumoto, Y., Wada‑Hiraike, O., Oda, K., Osuga, Y., Fujii, T."Clinical significance of Gremlin 1 in cervical cancer and its effects on cancer stem cell maintenance". Oncology Reports 35.1 (2016): 391-397.
Chicago
Sato, M., Kawana, K., Fujimoto, A., Yoshida, M., Nakamura, H., Nishida, H., Inoue, T., Taguchi, A., Takahashi, J., Adachi, K., Nagasaka, K., Matsumoto, Y., Wada‑Hiraike, O., Oda, K., Osuga, Y., Fujii, T."Clinical significance of Gremlin 1 in cervical cancer and its effects on cancer stem cell maintenance". Oncology Reports 35, no. 1 (2016): 391-397. https://doi.org/10.3892/or.2015.4367