Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 44, Issue 4, Pages 1376-1384Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2014.2265
Keywords
fibronectin; 5-fluorouracil; cell adhesion-mediated drug resistance; oral squamous cell carcinoma
Categories
Funding
- Japan Society for the Promotion of Science [21792017]
- Grants-in-Aid for Scientific Research [25461918, 21792017, 23592967] Funding Source: KAKEN
Ask authors/readers for more resources
The tumor-associated microenvironment has been shown to protect tumor cells from treatment, and the extra-cellular 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 1 integrin-mediated survival regulators such as ILK, Akt and NF-B. In addition, we investigated whether FNIII14, a 22-mer peptide derived from FN that potently prevents 1 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 over-expressed 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-B 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-B 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available