Istradefylline induces A2A/P2X7 crosstalk expression inducing pro-inflammatory signal, and reduces AKT/mTOR signaling in melanoma-bearing mice

Silva, Jean Lucas Gutknecht da; Passos, Daniela F.; Cabral, Fernanda Licker; Miron, Vanessa Valéria; Schetinger, Maria Rosa Chitolina; Cardoso, Antônio Américo; Piva, Camila Jesus; Gomes, Celso; Ebone, Renan Silva; Leal, Daniela Bitencourt Rosa

doi:10.1007/s12032-023-02033-6

Cited by 3 publications

(1 citation statement)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, inside tumors, A2AR was incremented in necrotic areas, thereby increasing neovascularization, and its blockade caused a substantial reduction in VEGF production in tumor-bearing P2X7 null mice [ 84 ]. In a similar vein, a recent study reported upregulation of the P2X7 receptor in melanoma-bearing mice treated with the A2AR antagonist istradefylline [ 150 ].…”

Section: P2x7r and Its Crosstalk With The Adenosinergic Axis In Cancermentioning

confidence: 91%

The P2X7 Receptor in Oncogenesis and Metastatic Dissemination: New Insights on Vesicular Release and Adenosinergic Crosstalk

Adinolfi,

De Marchi,

Grignolo

et al. 2023

IJMS

View full text Add to dashboard Cite

The tumor niche is an environment rich in extracellular ATP (eATP) where purinergic receptors have essential roles in different cell subtypes, including cancer, immune, and stromal cells. Here, we give an overview of recent discoveries regarding the role of probably the best-characterized purinergic receptor in the tumor microenvironment: P2X7. We cover the activities of the P2X7 receptor and its human splice variants in solid and liquid cancer proliferation, dissemination, and crosstalk with immune and endothelial cells. Particular attention is paid to the P2X7-dependent release of microvesicles and exosomes, their content, including ATP and miRNAs, and, in general, P2X7-activated mechanisms favoring metastatic spread and niche conditioning. Moreover, the emerging role of P2X7 in influencing the adenosinergic axis, formed by the ectonucleotidases CD39 and CD73 and the adenosine receptor A2A in cancer, is analyzed. Finally, we cover how antitumor therapy responses can be influenced by or can change P2X7 expression and function. This converging evidence suggests that P2X7 is an attractive therapeutic target for oncological conditions.

show abstract

Section: P2x7r and Its Crosstalk With The Adenosinergic Axis In Cancermentioning

confidence: 91%

The P2X7 Receptor in Oncogenesis and Metastatic Dissemination: New Insights on Vesicular Release and Adenosinergic Crosstalk

Adinolfi,

De Marchi,

Grignolo

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

Hypoxia-adenosinergic regulation of B cell responses

Pruitt,

Abbott

2024

Front. Immunol.

View full text Add to dashboard Cite

Hypoxic microenvironments induce widespread metabolic changes that have been shown to be critical in regulating innate and adaptive immune responses. Hypoxia-induced changes include the generation of extracellular adenosine followed by subsequent signaling through adenosine receptors on immune cells. This evolutionarily conserved “hypoxia-adenosinergic” pathway of hypoxia → extracellular adenosine → adenosine receptor signaling has been shown to be critical in limiting and redirecting T cell responses including in tumor microenvironments and the gut mucosa. However, the question of whether hypoxic microenvironments are involved in the development of B cell responses has remained unexplored until recently. The discovery that germinal centers (GC), the anatomic site in which B cells undergo secondary diversification and affinity maturation, develop a hypoxic microenvironment has sparked new interest in how this evolutionarily conserved pathway affects antibody responses. In this review we will summarize what is known about hypoxia-adenosinergic microenvironments in lymphocyte development and ongoing immune responses. Specific focus will be placed on new developments regarding the role of the hypoxia-adenosinergic pathway in regulating GC development and humoral immunity.

show abstract

Targeting the Adenosine A2A Receptor as a Novel Therapeutic Approach for Renal Cell Carcinoma: Mechanisms and Clinical Trial Review

Chen,

Chang,

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

Renal cell carcinoma (RCC) accounts for nearly 2% of cancers diagnosed worldwide. For metastatic RCC, targeted therapy is one of the most common treatment methods. It can include approaches that target vascular endothelial growth factor (VEGFR) or rely on immune checkpoint inhibitors or mTOR inhibitors. Adenosine A2A receptor (A2AR) is a type of widely distributed G-protein-coupled receptor (GPCR). Recently, an increasing number of studies suggest that the activation of A2AR can downregulate anti-tumor immune responses and prevent tumor growth. Currently, the data on A2AR antagonists in RCC treatment are still limited. Therefore, in this article, we further investigate the clinical trials investigating A2AR drugs in RCC. We also describe the epidemiology and current treatment of RCC, along with the physiological role of A2AR, and the types of A2AR drugs that are associated with tumor treatment.

show abstract

Istradefylline induces A2A/P2X7 crosstalk expression inducing pro-inflammatory signal, and reduces AKT/mTOR signaling in melanoma-bearing mice

Cited by 3 publications

References 53 publications

The P2X7 Receptor in Oncogenesis and Metastatic Dissemination: New Insights on Vesicular Release and Adenosinergic Crosstalk

The P2X7 Receptor in Oncogenesis and Metastatic Dissemination: New Insights on Vesicular Release and Adenosinergic Crosstalk

Hypoxia-adenosinergic regulation of B cell responses

Targeting the Adenosine A2A Receptor as a Novel Therapeutic Approach for Renal Cell Carcinoma: Mechanisms and Clinical Trial Review

Contact Info

Product

Resources

About