ArticleOncotarget2016
Activation of the A2B adenosine receptor in B16 melanomas induces CXCL12 expression in FAP-positive tumor stromal cells, enhancing tumor progression.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Discovery of Potent 1,3-Cyclobutane-Containing Dual AACS medicinal chemistry letters · 2026Article
- Adenosine signaling in tumor immune escape: metabolic checkpoints, myeloid suppression, and combination immunotherapy.Frontiers in oncology · 2026Review
- Melanoma and its fibroblastic allies: the emerging importance of CAFs in immune suppression, ECM modulation, and therapy resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- The progress and prospects of targeting the adenosine pathway in cancer immunotherapy.Biomarker research · 2025Review
- Potential of Adora2b as an immunotherapeutic target for gastric cancer.Frontiers in immunology · 2025Review
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- Advances in targeting cancer-associated fibroblasts through single-cell spatial transcriptomic sequencing.Biomarker research · 2024Review
- Melanoma-associated fibroblasts in tumor-promotion flammation and antitumor immunity: novel mechanisms and potential immunotherapeutic strategies.Human molecular genetics · 2024Review
- The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies.Acta pharmaceutica Sinica. B · 2024Review
- Article
- Inhibitors of the CD73-adenosinergic checkpoint as promising combinatory agents for conventional and advanced cancer immunotherapy.Frontiers in immunology · 2023Review
- Blocking the AAnnals of medicine · 2022Article
- Immunotherapy: Reshape the Tumor Immune Microenvironment.Frontiers in immunology · 2022Review
- Fibroblast Activation Protein-α as a Target in the Bench-to-Bedside Diagnosis and Treatment of Tumors: A Narrative Review.Frontiers in oncology · 2021Review
- Evaluation of Combination Strategies for the AFrontiers in immunology · 2021Article
- CD38 in cancer-associated fibroblasts promotes pro-tumoral activity.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- The adenosine pathway in immuno-oncology.Nature reviews. Clinical oncology · 2020Review
- The role of fibroblast activation protein in health and malignancy.Cancer metastasis reviews · 2020Review
- Extracellular Adenine Nucleotides and Adenosine Modulate the Growth and Survival of THP-1 Leukemia Cells.International journal of molecular sciences · 2020Article
- The role of cancer-associated fibroblasts in renal cell carcinoma. An example of tumor modulation through tumor/non-tumor cell interactions.Journal of advanced research · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The A2B receptor (A2BR) can mediate adenosine-induced tumor proliferation, immunosuppression and angiogenesis. Targeting the A2BR has proved to be therapeutically effective in some murine tumor models, but the mechanisms of these effects are still incompletely understood. Here, we report that pharmacologic inhibition of A2BR with PSB1115, which inhibits tumor growth, decreased the number of fibroblast activation protein (FAP)-expressing cells in tumors in a mouse model of melanoma. This effect was associated with reduced expression of fibroblast growth factor (FGF)-2. Treatment of melanoma-associated fibroblasts with the A2BR agonist Bay60-6583 enhanced CXCL12 and FGF2 expression. This effect was abrogated by PSB1115. The A2AR agonist CGS21680 did not induce CXCL12 or FGF2 expression in tumor associated fibroblasts. Similar results were obtained under hypoxic conditions in skin-derived fibroblasts, which responded to Bay60-6583 in an A2BR-dependent manner, by stimulating pERK1/2. FGF2 produced by Bay60-6583-treated fibroblasts directly enhanced the proliferation of melanoma cells. This effect could be reversed by PSB1115 or an anti-FGF2 antibody. Interestingly, melanoma growth in mice receiving Bay60-6583 was attenuated by inhibition of the CXCL12/CXCR4 pathway with AMD3100. CXCL12 and its receptor CXCR4 are involved in angiogenesis and immune-suppression. Treatment of mice with AMD3100 reduced the number of CD31+ cells induced by Bay60-6583. Conversely, CXCR4 blockade did not affect the accumulation of tumor-infiltrating MDSCs or Tregs. Together, our data reveal an important role for A2BR in stimulating FGF2 and CXCL12 expression in melanoma-associated fibroblasts. These factors contribute to create a tumor-promoting microenvironment. Our findings support the therapeutic potential of PSB1115 for melanoma.
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