Adenosine receptor 2B activity promotes autonomous growth, migration as well as vascularization of head and neck squamous cell carcinoma cells.
5'-Nucleotidase
/ biosynthesis
Adenosine A2 Receptor Antagonists
/ pharmacology
Animals
Apoptosis
/ drug effects
Cell Cycle Checkpoints
/ drug effects
Cell Growth Processes
/ drug effects
Cell Line, Tumor
Cell Movement
/ drug effects
Chick Embryo
Chorioallantoic Membrane
/ metabolism
GPI-Linked Proteins
/ biosynthesis
Head and Neck Neoplasms
/ blood supply
Humans
Jurkat Cells
Neovascularization, Pathologic
/ metabolism
Receptor, Adenosine A2B
/ biosynthesis
Squamous Cell Carcinoma of Head and Neck
/ blood supply
Sulfonamides
/ pharmacology
Xanthines
/ pharmacology
ADORA2B
CD39
CD73
HNSCC
adenosine
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
21
12
2018
revised:
21
11
2019
accepted:
05
12
2019
pubmed:
18
12
2019
medline:
24
3
2021
entrez:
18
12
2019
Statut:
ppublish
Résumé
Adenosine is a signaling molecule that exerts dual effects on tumor growth: while it inhibits immune cell function and thereby prevents surveillance by the immune system, it influences tumorigenesis directly via activation of adenosine receptors on tumor cells at the same time. However, the adenosine-mediated mechanisms affecting oncogenic processes particularly in head and neck squamous cell carcinomas (HNSCC) are not fully understood. Here, we investigated the role of adenosine receptor activity on HNSCC-derived cell lines. Targeting the adenosine receptor A2B (ADORA2B) on these cells with the inverse agonist/antagonist PSB-603 leads to inhibition of cell proliferation, transmigration as well as VEGFA secretion in vitro. At the molecular level, these effects were associated with cell cycle arrest as well as the induction of the apoptotic pathway. In addition, shRNA-mediated downmodulation of ADORA2B expression caused decreased proliferation. Moreover, in in vivo xenograft experiments, chemical and genetic abrogation of ADORA2B activity impaired tumor growth associated with decreased tumor vascularization. Together, our findings characterize ADORA2B as a crucial player in the maintenance of HNSCC and, therefore, as a potential therapeutic target for HNSCC treatment.
Substances chimiques
ADORA2B protein, human
0
Adenosine A2 Receptor Antagonists
0
GPI-Linked Proteins
0
PSB603
0
Receptor, Adenosine A2B
0
Sulfonamides
0
Xanthines
0
5'-Nucleotidase
EC 3.1.3.5
NT5E protein, human
EC 3.1.3.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
202-217Informations de copyright
© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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