Adenosine A2b receptor promotes progression of human oral cancer

BMC Cancer

Research Article

Katsunori Ogawara¹  Atsushi Kasamatsu¹  Yosuke Sakamoto¹  Masashi Shiiba²  Hiroki Kasama³  Yasuyuki Minakawa³  Tomoyoshi Koyama³  Atsushi Okamoto³  Katsuhiro Uzawa⁴  Hideki Tanzawa⁴  Hidetaka Yokoe⁵ 

[1] Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, 260-8670, Chuo-ku, Chiba, Japan;Department of Medical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, 260-8670, Chuo-ku, Chiba, Japan;Department of Oral Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, 260-8670, Chuo-ku, Chiba, Japan;Department of Oral Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, 260-8670, Chuo-ku, Chiba, Japan;Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, 260-8670, Chuo-ku, Chiba, Japan;Department of Oral and Maxillofacial Surgery Research Institute, National Defense Medical College Hospital, 3-2, Namiki, 359-8513, Tokorozawa-shi, Saitama, Japan;

关键词: Oral Squamous Cell Carcinoma;    Adenosine Receptor;    Oral Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma Cell;    Oral Squamous Cell Carcinoma Tissue;   

DOI  :  10.1186/s12885-015-1577-2

 received in 2014-09-17, accepted in 2015-07-27,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundAdenosine A2b receptor (ADORA2B) encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. Little is known about the relevance of ADORA2B to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of ADORA2B in OSCC.MethodsThe ADORA2B expression levels in nine OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Using an ADORA2B knockdown model, we assessed cellular proliferation and expression of hypoxia-inducible factor1α (HIF-1α). We examined the adenosine receptor expression profile under both normoxic and hypoxic conditions in the OSCC-derived cells. In addition to in vitro data, the clinical correlation between the ADORA2B expression levels in primary OSCCs (n = 100 patients) and the clinicopathological status by immunohistochemistry (IHC) also was evaluated.ResultsADORA2B mRNA and protein were up-regulated significantly (p < 0.05) in seven OSCC-derived cells compared with human normal oral keratinocytes. Suppression of ADORA2B expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells. HIF-1α also was down-regulated in ADORA2B knockdown OSCC cells. During hypoxia, ADORA2B expression was induced significantly (p < 0.05) in the mRNA and protein after 24 hours of incubation in OSCC-derived cells. IHC showed that ADORA2B expression in primary OSCCs was significantly (p < 0.05) greater than in the normal oral counterparts and that ADORA2B-positive OSCCs were correlated closely (p < 0.05) with tumoral size.ConclusionOur results suggested that ADORA2B controls cellular proliferation via HIF-1α activation, indicating that ADORA2B may be a key regulator of tumoral progression in OSCCs.

【 授权许可】

Unknown   
© Kasama et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.