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DOI: 10.1055/s-0038-1640205
Analysis of the influence of adenosine on HNSCC cell lines
Introduction:
HNSCC (head and neck squamous cell carcinoma) is the fifth most common cancer worldwide. Despite advances in the treatment of these tumors, the 5-year survival rate has hardly changed in the last 20 years. Various studies identified adenosine as an important regulating autocrine and paracrine factor for neoplastic tissue. For entities such as breast and prostate cancer it has been shown that tumor progression and metastasis is affected by direct influence of adenosine on tumor cells. Therefore, the influence of adenosine on HNSCC cell lines was investigated.
Methods:
First, the ADORA (adenosine receptor) expression profile was analyzed by RT-PCR and Western-Blot. Second, the effects of ADORA modulation by receptor ligands on proliferation, migration, invasion and angiogenesis were investigated. In vitro experiments involved MTT assays, scratch assays, transwell assays and VEGF-ELISA, in vivo experiments involved tumor xenograft on chicken chorionallantoic membranes (CAM-Assay).
Results:
It was found that ADORA2B is expressed by all HNSCC cell lines while the other ADORA subtypes were below the detection limit. Inhibition of ADORA2B by the specific inverse agonist PSB603 resulted in impaired proliferation, migration, VEGF secretion and augmented apoptosis in vitro as well as impaired tumor growth and decreased blood vessel formation in vivo.
Conclusion:
The strong inhibitory effect of the inverse agonist PSB603 on the HNSCC cell lines suggests that ADORA2B is present as a constitutively activated receptor in the HNSCC cell lines and thus promotes tumor progression independently of ligands. To that effect, targeted inhibition of ADORA2B could represent a new promising approach in the therapy of HNSCC.
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No conflict of interest has been declared by the author(s).
Publication History
Publication Date:
18 April 2018 (online)
© 2018. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Georg Thieme Verlag KG
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