ArticleOncogene2015
Differential impact of adenosine nucleotides released by osteocytes on breast cancer growth and bone metastasis.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 111 citations in OpenAlex.
- Role of the P2X7 receptor in breast cancer progression.Purinergic signalling · 2025Review
- Review
- Connexin 43 hemichannels and related diseases.Antibody therapeutics · 2024Review
- SOST/Sclerostin impairs the osteogenesis and angiogesis in glucocorticoid-associated osteonecrosis of femoral head.Molecular medicine (Cambridge, Mass.) · 2024Article
- High-affinity agonism at the P2XNature communications · 2024Article
- Antibody-activation of connexin hemichannels in bone osteocytes with ATP release suppresses breast cancer and osteosarcoma malignancy.Cell reports · 2024Article
- Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity.Science advances · 2024Article
- Volume-regulated anion channels conduct ATP in undifferentiated mammary cells and promote tumorigenesis in xenograft nude mouse.Frontiers in cell and developmental biology · 2024Article
- Discovery of a potent, selective, and tumor-suppressing antibody antagonist of adenosine A2A receptor.PloS one · 2024Article
- Istradefylline modulates purinergic enzymes and reduces malignancy-associated factors in B16F10 melanoma cells.Purinergic signalling · 2023Article
- A Population of Tumor-Infiltrating CD4+ T Cells Co-Expressing CD38 and CD39 Is Associated with Checkpoint Inhibitor Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Bone-homing metastatic breast cancer cells impair osteocytes' mechanoresponse in a 3D loading model.Heliyon · 2023Article
- Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.Bone reports · 2023Article
- Review
- Animal Models for the Investigation of P2X7 Receptors.International journal of molecular sciences · 2023Review
- P2X7 receptor involved in antitumor activity of atractylenolide I in human cervical cancer cells.Purinergic signalling · 2023Article
- Reduction of breast cancer extravasation via vibration activated osteocyte regulation.iScience · 2022Article
- Microfluidic Co-culture Platforms for Studying Osteocyte Regulation of Other Cell Types under Dynamic Mechanical Stimulation.Current osteoporosis reports · 2022Review
- Design, Synthesis, and Biological Evaluation of Novel Dihydropyridine and Pyridine Analogs as Potent Human Tissue Nonspecific Alkaline Phosphatase Inhibitors with Anticancer Activity: ROS and DNA Damage-Induced Apoptosis.Molecules (Basel, Switzerland) · 2022Article
- Association of adenosine signaling gene signature with estrogen receptor-positive breast and prostate cancer bone metastasis.Frontiers in medicine · 2022Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Extracellular ATP has been shown to either inhibit or promote cancer growth and migration; however, the mechanism underlying this discrepancy remained elusive. Here we demonstrate the divergent roles of ATP and adenosine released by bone osteocytes on breast cancers. We showed that conditioned media (CM) collected from osteocytes treated with alendronate (AD), a bisphosphonate drug, inhibited the migration of human breast cancer MDA-MB-231 cells. Removal of the extracellular ATP by apyrase in CM abolished this effect, suggesting the involvement of ATP. ATP exerted its inhibitory effect through the activation of purinergic P2X receptor signaling in breast cancer cells evidenced by the attenuation of the inhibition by an antagonist, oxidized ATP, as well as knocking down P2X7 with small interfering RNA (siRNA), and the inhibition of migration by an agonist, BzATP. Intriguingly, ATP had a biphasic effect on breast cancer cells-lower dosage inhibited but higher dosage promoted its migration. The stimulatory effect on migration was blocked by an adenosine receptor antagonist, MRS1754, ARL67156, an ecto-ATPase inhibitor, and A2A receptor siRNA, suggesting that in contrast to ATP, adenosine, a metabolic product of ATP, promoted migration of breast cancer cells. Consistently, non-hydrolyzable ATP, ATPγS, only inhibited but did not promote cancer cell migration. ATP also had a similar inhibitory effect on the Py8119 mouse mammary carcinoma cells; however, adenosine had no effect owing to the absence of the A2A receptor. Consistently, ATPγS inhibited, whereas adenosine promoted anchorage-independent growth of MDA-MB-231 cells. Our in vivo xenograft study showed a significant delay of tumor growth with the treatment of ATPγS. Moreover, the extent of bone metastasis in a mouse intratibial model was significantly reduced with the treatment of ATPγS. Together, our results suggest the distinct roles of ATP and adenosine released by osteocytes and the activation of corresponding receptors P2X7 and A2A signaling on breast cancer cell growth, migration and bone metastasis.
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