PMID- 24452447
OWN - NLM
STAT- MEDLINE
DCOM- 20141126
LR  - 20211203
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 44
IP  - 4
DP  - 2014 Apr
TI  - Overexpression of fibronectin confers cell adhesion-mediated drug resistance 
      (CAM-DR) against 5-FU in oral squamous cell carcinoma cells.
PG  - 1376-84
LID - 10.3892/ijo.2014.2265 [doi]
AB  - 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 beta1 integrin-mediated survival regulators such as ILK, Akt and 
      NF-kappaB. In addition, we investigated whether FNIII14, a 22-mer peptide derived 
      from FN that potently prevents beta1 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-kappaB 
      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-kappaB 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.
FAU - Nakagawa, Yoshihiro
AU  - Nakagawa Y
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Nakayama, Hideki
AU  - Nakayama H
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Nagata, Masashi
AU  - Nagata M
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Yoshida, Ryoji
AU  - Yoshida R
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Kawahara, Kenta
AU  - Kawahara K
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Hirosue, Akiyuki
AU  - Hirosue A
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Tanaka, Takuya
AU  - Tanaka T
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Yuno, Akira
AU  - Yuno A
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Matsuoka, Yuichiro
AU  - Matsuoka Y
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Kojima, Taku
AU  - Kojima T
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Yoshitake, Yoshihiro
AU  - Yoshitake Y
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Hiraki, Akimitsu
AU  - Hiraki A
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Shinohara, Masanori
AU  - Shinohara M
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto 
      University, Chuo-ku, Kumamoto 860-8556, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140121
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Fibronectins)
RN  - 0 (Integrin beta1)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.1.- (integrin-linked kinase)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Antimetabolites, Antineoplastic/pharmacology
MH  - Apoptosis/physiology
MH  - Biomarkers, Tumor
MH  - Carcinoma, Squamous Cell/drug therapy
MH  - Cell Adhesion/drug effects/*genetics
MH  - Cell Line, Tumor
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Extracellular Matrix/drug effects
MH  - Fibronectins/biosynthesis/*genetics
MH  - Fluorouracil/*pharmacology
MH  - Humans
MH  - Integrin beta1/metabolism
MH  - Mouth Neoplasms/*drug therapy
MH  - NF-kappa B/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - Tumor Microenvironment
EDAT- 2014/01/24 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/01/24 06:00
PHST- 2013/11/01 00:00 [received]
PHST- 2014/01/11 00:00 [accepted]
PHST- 2014/01/24 06:00 [entrez]
PHST- 2014/01/24 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.3892/ijo.2014.2265 [doi]
PST - ppublish
SO  - Int J Oncol. 2014 Apr;44(4):1376-84. doi: 10.3892/ijo.2014.2265. Epub 2014 Jan 
      21.