ArticleInternational journal of molecular sciences2022
CD73/Adenosine Pathway Involvement in the Interaction of Non-Small Cell Lung Cancer Stem Cells and Bone Cells in the Pre-Metastatic Niche.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Osteoclasts affect the anti-cancer activity of NK cells.Frontiers in immunology · 2026Article
- Extracellular Adenosine in Gastric Cancer: The Role of GCSCs.International journal of molecular sciences · 2025Article
- Recent Advancements in Lung Cancer Metastasis Prevention Based on Nanostrategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Review
- Purinergic system in cancer stem cells.Purinergic signalling · 2025Review
- Multi-stage mechanisms of tumor metastasis and therapeutic strategies.Signal transduction and targeted therapy · 2024Review
- The Adenosinergic Pathway in Non-Small Cell Lung Cancer.Cancers · 2024Review
- Translational Experimental Basis of Indirect Adenosine Receptor Agonist Stimulation for Bone Regeneration: A Review.International journal of molecular sciences · 2024Review
- Cellular and molecular characteristics of the premetastatic niches.Animal models and experimental medicine · 2023Review
- Evolving roles of CD38 metabolism in solid tumour microenvironment.British journal of cancer · 2023Review
- The road of NSCLC stem cells toward bone metastases.Bone reports · 2022Article
- Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Adenosinergic signaling is an important regulator of tissue homeostasis and extracellular accumulation of adenosine (Ado) and is associated with different pathologies, such as cancer. In non-small-cell lung cancer (NSCLC), a subset of CD133/CXCR4+ cancer stem cell (CSCs) has been demonstrated to initiate bone metastases. Here we investigated how NSCLC CSCs interact with osteoclasts (OCs) and osteoblasts (OBs) by modulating Ado production and OC activity. We proved that CSC-spheres, generated in vitro from NSCLC cell lines, express CD38, PC-1, and CD73, enzymes of the non-canonical adenosinergic pathway, produce high level of Ado, and down-regulate A1R and A3R inhibitory receptors, while expressing A2AR and A2BR. To address the Ado role and modulation of the in-bone pre-metastatic niche, we performed co-cultures of CSC-spheres with OCs and OBs cells. Firstly, we verified that active OCs do not activate non-canonical the adenosinergic pathway, conversely to OBs. OCs co-cultured with CSC-spheres increase Ado production that is related to the OC resorption activity and contributes to T-cell suppression. Finally, we proved the efficacy of anti-CD73 agents in blocking NSCLC cell migration. Overall, we assessed the importance of adenosinergic signaling in the interaction between CSCs and OCs at the pre-metastatic niche, with therapeutic implications related to Ado production.
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