Association of Expression of Receptor for Advanced Glycation End Products and Invasive Activity of Oral Squamous Cell Carcinoma

Vol. 69, No. 3, 2005

Free Abstract Article (Fulltext) Article (PDF 469 KB)

Laboratory/Clinical Translational Research

Association of Expression of Receptor for Advanced Glycation End Products and Invasive Activity of Oral Squamous Cell Carcinoma
Ujjal K. Bhawal^{a, f}, Yoshie Ozaki^b, Masahiro Nishimura^b, Masaru Sugiyama^c, Tomonori Sasahira^h, Yuji Nomura^d, Fuyuki Sato^a, Katsumi Fujimoto^a, Nobuyuki Sasakiⁱ, Masa-Aki Ikeda^g, Koichiro Tsuji^e, Hiroki Kuniyasu^h, Yukio Kato^a

Departments of
^aDental and Medical Biochemistry,
^bProsthetic Dentistry,
^cOral and Maxillofacial Surgery and
^dBiomaterials Science, Graduate School of Biomedical Sciences, Hiroshima University and
^eTwo Cells Co. Ltd., Hiroshima,
^fResearch and Development, Dentsply-Sankin KK and
^gSection of Molecular Embryology, Tokyo Medical and Dental University, Tokyo,
^hDepartment of Molecular Pathology, Nara Medical University, Kashihara, and
ⁱDepartment of Neuropsychiatry, Sapporo Medical University, Sapporo, Japan

Address of Corresponding Author

Oncology 2005;69:246-255 (DOI: 10.1159/000087910)

Key Words

Receptor for advanced glycation end products
Oral cancer
Invasion
Metastasis

Abstract

Objectives: 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.

Author Contacts

Ujjal K. Bhawal
Department of Dental and Medical Biochemistry
Graduate School of Biomedical Sciences, Hiroshima University
Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553 (Japan)
Tel. +81 82 257 5749, Fax +81 82 257 5749, E-Mail bhawal2002@yahoo.co.in

Article Information

Received: October 31, 2004
Accepted after revision: May 4, 2005
Published online: August 26, 2005
Number of Print Pages : 10
Number of Figures : 8, Number of Tables : 0, Number of References : 20

Medline Abstract (ID 16127291)

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