ArticleNeoplasia (New York, N.Y.)2011
Vascular CD39/ENTPD1 directly promotes tumor cell growth by scavenging extracellular adenosine triphosphate.
Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 136 citations in OpenAlex.
- Targeting CD39 as a Therapeutic for Cancer Immunotherapy.Expert reviews in molecular medicine · 2026Review
- The CD73-adenosine axis in melanoma: from multidimensional regulation to precision immunotherapy.Frontiers in immunology · 2026Review
- A novel tumor microenvironment-related gene signature for prognostic prediction of intrahepatic cholangiocarcinoma.Scientific reports · 2025Article
- Oxygen-carrying nanoemulsions and respiratory hyperoxia eliminate tumor hypoxia-induced immunosuppression.JCI insight · 2025Article
- Immunogenic Cell Death-related Signature Evaluates the Tumor Microenvironment and Predicts the Prognosis in Diffuse Large B-Cell Lymphoma.Biochemical genetics · 2025Article
- Microalgae-Derived Carotenoid Extract and Biomass Reduce Viability, Induce Oxidative Stress, and Modulate the Purinergic System in Two Melanoma Cell Lines.Life (Basel, Switzerland) · 2025Article
- Cd39 and P2rx7-Wnt signaling enhance blast pathogenicity in an experimental model of acute myeloid leukemia.Haematologica · 2025Article
- Chromosomal instability as a driver of cancer progression.Nature reviews. Genetics · 2025Review
- Purinergic Signaling in Non-Parenchymal Liver Cells.International journal of molecular sciences · 2024Review
- Platelets induce CD39 expression in tumor cells to facilitate tumor metastasis.British journal of cancer · 2024Article
- Exploring the metastasis-related biomarker and carcinogenic mechanism in liver cancer based on single cell technology.Heliyon · 2024Article
- Regulatory role of CD39 and CD73 in tumor immunity.Future oncology (London, England) · 2024Review
- CD39American journal of cancer research · 2024Article
- Istradefylline modulates purinergic enzymes and reduces malignancy-associated factors in B16F10 melanoma cells.Purinergic signalling · 2023Article
- Crosstalk of Immune Cells and Platelets in an Ovarian Cancer Microenvironment and Their Prognostic Significance.International journal of molecular sciences · 2023Review
- Focal Cryo-Immunotherapy with Intratumoral IL-12 Prevents Recurrence of Large Murine Tumors.Cancers · 2023Article
- Ion channel P2X7 receptor in the progression of cancer.Frontiers in oncology · 2023Review
- The ATP-dependent Pathways and Human Diseases.Current medicinal chemistry · 2023Article
- Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia.Frontiers in oncology · 2023Review
- Unlocking antitumor immunity with adenosine receptor blockers.Cancer drug resistance (Alhambra, Calif.) · 2023Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Extracellular adenosine triphosphate (ATP) is known to boost immune responses in the tumor microenvironment but might also contribute directly to cancer cell death. CD39/ENTPD1 is the dominant ectonucleotidase expressed by endothelial cells and regulatory T cells and catalyzes the sequential hydrolysis of ATP to AMP that is further degraded to adenosine by CD73/ecto-5'-nucleotidase. We have previously shown that deletion of Cd39 results in decreased growth of transplanted tumors in mice, as a result of both defective angiogenesis and heightened innate immune responses (secondary to loss of adenosinergic immune suppression). Whether alterations in local extracellular ATP and adenosine levels as a result of CD39 bioactivity directly affect tumor growth and cytotoxicity has not been investigated to date. We show here that extracellular ATP exerts antitumor activity by directly inhibiting cell proliferation and promoting cancer cell death. ATP-induced antiproliferative effects and cell death are, in large part, mediated through P2X(7) receptor signaling. Tumors in Cd39 null mice exhibit increased necrosis in association with P2X(7) expression. We further demonstrate that exogenous soluble NTPDase, or CD39 expression by cocultured liver sinusoidal endothelial cells, stimulates tumor cell proliferation and limits cell death triggered by extracellular ATP. Collectively, our findings indicate that local expression of CD39 directly promotes tumor cell growth by scavenging extracellular ATP. Pharmacological or targeted inhibition of CD39 enzymatic activity may find utility as an adjunct therapy in cancer management.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.