Regulatory T cells function at the early stage of tumor progression in a mouse model of tongue squamous cell carcinoma.
The objective of this study was to observe the distribution of regulatory T cells (Tregs) in the development of tongue squamous cell carcinoma (SCC) and to determine the role of Tregs in the progression of tongue SCC. A mouse model of 4-nitroquinoline-1-oxide (4NQO)-induced-tongue SCC was established. The expression of Forkhead box P3 (Foxp3), interleukin 10, transforming growth factor-β, chemokine CC motif ligands 17, 20, and CC chemokine receptor 4 was determined using real-time quantitative polymerase chain reaction. Foxp3 expression was also analyzed using immunohistochemistry. The results were compared with those of control mice and of 4NQO-treated mice treated with a cyclooxygenase-2 (COX-2) inhibitor. Well to moderately differentiated tongue SCC was induced in all of the experimental mice. The amount of Tregs of the experimental mice was over 10 times as much as control mice at the early stage of tumor progression. COX-2 inhibitor did not prevent the progression of tongue SCC and did not reduce the total amount of Tregs. Tregs function at the early stage of the development of tongue SCC, and it may be effective to suppress Tregs at the early stage of tumor progression for the treatment and/or prevention of tongue SCC.
Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Kentaro
K
Miki
Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. y.orita@live.jp.
Yorihisa
Y
Orita
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Yuka
Y
Gion
Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Soshi
S
Takao
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Kyotaro
K
Ohno
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Mai
M
Takeuchi
Department of Immunology, Nara Medical University, Nara, Japan.
Toshihiro
T
Ito
Department of Head and Neck, Shikoku Cancer Center, Ehime, Japan.
Hiroyuki
H
Hanakawa
Department of Otolaryngology, Head and Neck Surgery, Himeji Red Cross Hospital, Hyogo, Japan.
Tomoyasu
T
Tachibana
Department of Otolaryngology Head and Neck Surgery, National Hospital Organization Okayama Medical Center, Okayama, Japan.
Hidenori
H
Marunaka
Department of Otolaryngology, Head and Neck Surgery, Himeji Red Cross Hospital, Hyogo, Japan.
Takuma
T
Makino
Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
Akira
A
Minoura
Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Akihiro
A
Matsukawa
Department of Otolaryngology, Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Kazunori
K
Nishizaki
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Tadashi
T
Yoshino
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.|Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama, Japan.
Yasuharu
Y
Sato
D015112:4-Nitroquinoline-1-oxide; D000818:Animals; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000235:genetics / Q000378:metabolism; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015363:Quinolones; D054398:Receptors, CCR4 / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014062:Tongue Neoplasms / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
C120195:4-nitroquinolone-1-oxide; C493447:CCL20 protein, mouse; C499538:Ccl17 protein, mouse; C515355:Ccr4 protein, mouse; D054414:Chemokine CCL17; D054418:Chemokine CCL20; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015363:Quinolones; D054398:Receptors, CCR4; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015112:4-Nitroquinoline-1-oxide
Foxp3; IL-10; Regulatory T cell; TGF-β; Tongue squamous cell carcinoma