| RRC ID |
44866
|
| 著者 |
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.
|
| タイトル |
Overexpression of fibronectin confers cell adhesion-mediated drug resistance (CAM-DR) against 5-FU in oral squamous cell carcinoma cells.
|
| ジャーナル |
Int J Oncol
|
| 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.
|
| 巻・号 |
44(4)
|
| ページ |
1376-84
|
| 公開日 |
2014-4-1
|
| DOI |
10.3892/ijo.2014.2265
|
| PMID |
24452447
|
| MeSH |
Antimetabolites, Antineoplastic / pharmacology
Apoptosis / physiology
Biomarkers, Tumor
Carcinoma, Squamous Cell / drug therapy
Cell Adhesion / drug effects
Cell Adhesion / genetics*
Cell Line, Tumor
Drug Resistance, Neoplasm / genetics*
Extracellular Matrix / drug effects
Fibronectins / biosynthesis
Fibronectins / genetics*
Fluorouracil / pharmacology*
Humans
Integrin beta1 / metabolism
Mouth Neoplasms / drug therapy*
NF-kappa B / metabolism
Protein Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction
Tumor Microenvironment
|
| IF |
3.899
|
| 引用数 |
27
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
Ca9-22(RCB1976)
SAS(RCB1974) |
