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Article

Overexpression of fibronectin confers cell adhesion‑mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells

  • Authors:
    • Yoshihiro Nakagawa
    • Hideki Nakayama
    • Masashi Nagata
    • Ryoji Yoshida
    • Kenta Kawahara
    • Akiyuki Hirosue
    • Takuya Tanaka
    • Akira Yuno
    • Yuichiro Matsuoka
    • Taku Kojima
    • Yoshihiro Yoshitake
    • Akimitsu Hiraki
    • Masanori Shinohara
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Chuo-ku, Kumamoto 860-8556, Japan
  • Pages: 1376-1384
    |
    Published online on: January 21, 2014
       https://doi.org/10.3892/ijo.2014.2265
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Abstract

The tumor-associated microenvironment has been shown to protect tumor cells from treatment, and the extracellular matrix (ECM) is known to affect drug resistance as a key regulator of the tumor microenvironment. However, little is known about cell adhesion-mediated drug resistance (CAM‑DR) due to cell-ECM contact in patients with oral squamous cell carcinoma (OSCC). In the present study, we evaluated the ECM molecule fibronectin (FN) using DNA microarray data obtained from parental and 5-FU-resistant OSCC cell lines. We investigated the effects of cell adhesion to FN on 5-FU resistance in OSCC cells and examined the activation of FN receptor β1 integrin‑mediated survival regulators such as ILK, Akt and NF-κB. In addition, we investigated whether FNIII14, a 22-mer peptide derived from FN that potently prevents β1 integrin-mediated adhesion to FN, could overcome CAM-DR against 5-FU in OSCC cells and examined the activation of survival regulators and apoptosis-related molecules. Consequently, we obtained the following results. FN was extracellularly overexpressed in the 5-FU-resistant cells compared with that observed in the 5-FU-sensitive cells. Cell adhesion to FN enhanced 5-FU resistance and activated integrin-mediated ILK/Akt/NF-κB survival signaling in the 5-FU-resistant OSCC cells. Furthermore, the inhibition of cell adhesion to FN by FNIII14 enhanced chemosensitivity to 5-FU and apoptosis by suppressing ILK/Akt/NF-κB signaling in the 5-FU-resistant cells. These novel findings demonstrate that FN is a potentially useful biomarker and therapeutic target for improving the treatment of OSCC, particularly in the setting of 5-FU resistance.
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Copy and paste a formatted citation
Spandidos Publications style
Nakagawa Y, Nakayama H, Nagata M, Yoshida R, Kawahara K, Hirosue A, Tanaka T, Yuno A, Matsuoka Y, Kojima T, Kojima T, et al: Overexpression of fibronectin confers cell adhesion‑mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells. Int J Oncol 44: 1376-1384, 2014.
APA
Nakagawa, Y., Nakayama, H., Nagata, M., Yoshida, R., Kawahara, K., Hirosue, A. ... Shinohara, M. (2014). Overexpression of fibronectin confers cell adhesion‑mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells. International Journal of Oncology, 44, 1376-1384. https://doi.org/10.3892/ijo.2014.2265
MLA
Nakagawa, Y., Nakayama, H., Nagata, M., Yoshida, R., Kawahara, K., Hirosue, A., Tanaka, T., Yuno, A., Matsuoka, Y., Kojima, T., Yoshitake, Y., Hiraki, A., Shinohara, M."Overexpression of fibronectin confers cell adhesion‑mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells". International Journal of Oncology 44.4 (2014): 1376-1384.
Chicago
Nakagawa, Y., Nakayama, H., Nagata, M., Yoshida, R., Kawahara, K., Hirosue, A., Tanaka, T., Yuno, A., Matsuoka, Y., Kojima, T., Yoshitake, Y., Hiraki, A., Shinohara, M."Overexpression of fibronectin confers cell adhesion‑mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells". International Journal of Oncology 44, no. 4 (2014): 1376-1384. https://doi.org/10.3892/ijo.2014.2265
Copy and paste a formatted citation
x
Spandidos Publications style
Nakagawa Y, Nakayama H, Nagata M, Yoshida R, Kawahara K, Hirosue A, Tanaka T, Yuno A, Matsuoka Y, Kojima T, Kojima T, et al: Overexpression of fibronectin confers cell adhesion‑mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells. Int J Oncol 44: 1376-1384, 2014.
APA
Nakagawa, Y., Nakayama, H., Nagata, M., Yoshida, R., Kawahara, K., Hirosue, A. ... Shinohara, M. (2014). Overexpression of fibronectin confers cell adhesion‑mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells. International Journal of Oncology, 44, 1376-1384. https://doi.org/10.3892/ijo.2014.2265
MLA
Nakagawa, Y., Nakayama, H., Nagata, M., Yoshida, R., Kawahara, K., Hirosue, A., Tanaka, T., Yuno, A., Matsuoka, Y., Kojima, T., Yoshitake, Y., Hiraki, A., Shinohara, M."Overexpression of fibronectin confers cell adhesion‑mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells". International Journal of Oncology 44.4 (2014): 1376-1384.
Chicago
Nakagawa, Y., Nakayama, H., Nagata, M., Yoshida, R., Kawahara, K., Hirosue, A., Tanaka, T., Yuno, A., Matsuoka, Y., Kojima, T., Yoshitake, Y., Hiraki, A., Shinohara, M."Overexpression of fibronectin confers cell adhesion‑mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells". International Journal of Oncology 44, no. 4 (2014): 1376-1384. https://doi.org/10.3892/ijo.2014.2265
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