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.
