Association of expression of receptor for advanced glycation end products and invasive activity of oral squamous cell carcinoma.
OBJECTIVE
The receptor for advanced glycation end products (RAGE) is a newly recognized factor regulating cancer cell invasion and metastasis. Nevertheless, the involvement of RAGE in the development and progression of oral squamous cell carcinomas has not been elucidated. This study investigated the expression of RAGE in ten oral squamous cell carcinoma cell lines including primary and metastatic cell lines and its association with invasion and metastasis.


METHODS
Reverse transcriptase-polymerase chain reaction, antisense phosphorothioate (S)-oligodeoxynucleotide assay, preparation of antibody, immunohistochemical staining, immunoblot analysis, migration assay, in vitro invasion assay, and wound-healing assay were used.


RESULTS
RAGE protein expression of metastatic cancer cells treated with RAGE antisense S-oligodeoxynucleotide was significantly reduced compared to that of sense S-oligodeoxynucleotide-treated cells. The migration assay showed that invasive activity was significantly reduced in metastatic cancer cells treated with RAGE antisense S-oligodeoxynucleotide. Similarly, during invasion assays, numbers of invading cells were also reduced with the addition of RAGE antisense S-oligodeoxynucleotide-treated cells. A wound-healing assay showed that only a few RAGE antisense S-oligodeoxynucleotide-treated cancer cells migrated into the scraped area, whereas sense S-oligodeoxynucleotide-treated cells showed many budding nests in the scraped area of the metastatic cell lines. Immunohistochemically, oral squamous cell carcinoma cells in the tumour mesenchymal border were often immunopositive, whereas basal cells in the normal mucosa were scarcely positive.


CONCLUSIONS
These results suggest that RAGE expression appears to be closely associated with the invasiveness of oral squamous cell carcinoma and represents a promising candidate for assessing the future therapeutic potential in treating patients with oral carcinoma.
Bhawal
Ujjal K
UK
Department of Dental and Medical Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. bhawal2002@yahoo.co.in
Ozaki
Yoshie
Y
Nishimura
Masahiro
M
Sugiyama
Masaru
M
Sasahira
Tomonori
T
Nomura
Yuji
Y
Sato
Fuyuki
F
Fujimoto
Katsumi
K
Sasaki
Nobuyuki
N
Ikeda
Masa-Aki
MA
Tsuji
Koichiro
K
Kuniyasu
Hiroki
H
Kato
Yukio
Y
D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D020319:Oligodeoxyribonucleotides, Antisense / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing
D015820:Cadherins; D017127:Glycation End Products, Advanced; D020319:Oligodeoxyribonucleotides, Antisense; D020780:Matrix Metalloproteinase 9