ArticleBMC cancer2015
Nitric oxide donors increase PVR/CD155 DNAM-1 ligand expression in multiple myeloma cells: role of DNA damage response activation.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 64 citations in OpenAlex.
- Epithelial CD155-TIGIT/CD226 signaling links CD8⁺ T-cell exhaustion to frequent exacerbations in COPD.Respiratory research · 2026Observational
- Plasticity and immune marker profiling of tumour- and ascites-derived microtumours in serous ovarian cancer: relevance for short-term culture models.Frontiers in immunology · 2026Article
- NECTIN4 regulates the cell surface expression of CD155 in non-small cell lung cancer cells and induces tumor resistance to PD-1 inhibitors.Cancer immunology, immunotherapy : CII · 2025Article
- Interplay of KIR2DL5, nitric oxide, and tobacco smoking in predisposition to bladder cancer.Frontiers in cell and developmental biology · 2025Article
- JS-K activates G2/M checkpoints through the DNA damage response and induces autophagy via CAMKKβ/AMPKα/mTOR pathway in bladder cancer cells.Journal of Cancer · 2024Article
- The Nectin family ligands, PVRL2 and PVR, in cancer immunology and immunotherapy.Frontiers in immunology · 2024Review
- MicroRNA-326 negatively regulates CD155 expression in lung adenocarcinoma.Cancer science · 2023Article
- Dysregulation of DNAM-1-Mediated NK Cell Anti-Cancer Responses in the Tumor Microenvironment.Cancers · 2023Review
- CD155 and Its Receptors as Targets for Cancer Therapy.International journal of molecular sciences · 2023Review
- T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis.Immunity · 2023Article
- Killer instincts: natural killer cells as multifactorial cancer immunotherapy.Frontiers in immunology · 2023Review
- Poliovirus receptor inhibition in breast cancer cells induces antitumor immunity via T cell activation.American journal of cancer research · 2023Article
- Opportunities for Nitric Oxide in Potentiating Cancer Immunotherapy.Pharmacological reviews · 2022Review
- Emergence of the CD226 Axis in Cancer Immunotherapy.Frontiers in immunology · 2022Review
- Perspectives on immune checkpoint ligands: expression, regulation, and clinical implications.BMB reports · 2021Review
- Overexpression of CD155 is associated with PD-1 and PD-L1 expression on immune cells, rather than tumor cells in the breast cancer microenvironment.World journal of clinical cases · 2020Article
- Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor.Cancers · 2020Article
- CD155 contributes to the mesenchymal phenotype of triple-negative breast cancer.Cancer science · 2020Article
- CD155: A Multi-Functional Molecule in Tumor Progression.International journal of molecular sciences · 2020Review
- Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDNAX accessory molecule-1 (DNAM-1) is an activating receptor constitutively expressed by macrophages/dendritic cells and by T lymphocytes and Natural Killer (NK) cells, having an important role in anticancer responses; in this regard, combination therapies able to enhance the expression of DNAM-1 ligands on tumor cells are of therapeutic interest. In this study, we investigated the effect of different nitric oxide (NO) donors on the expression of the DNAM-1 ligand Poliovirus Receptor/CD155 (PVR/CD155) in multiple myeloma (MM) cells.
methodsSix MM cell lines, SKO-007(J3), U266, OPM-2, RPMI-8226, ARK and LP1 were used to investigate the activity of different nitric oxide donors [DETA-NO and the NO-releasing prodrugs NCX4040 (NO-aspirin) and JS-K] on the expression of PVR/CD155, using Flow Cytometry and Real-Time PCR. Western-blot and specific inhibitors were employed to investigate the role of soluble guanylyl cyclase/cGMP and activation of the DNA damage response (DDR).
resultsOur results indicate that increased levels of nitric oxide can upregulate PVR/CD155 cell surface and mRNA expression in MM cells; in addition, exposure to nitric oxide donors renders myeloma cells more efficient to activate NK cell degranulation and enhances their ability to trigger NK cell-mediated cytotoxicity. We found that activation of the soluble guanylyl cyclase and increased cGMP concentrations by nitric oxide is not involved in the up-regulation of ligand expression. On the contrary, treatment of MM cells with nitric oxide donors correlated with the activation of a DNA damage response pathway and inhibition of the ATM /ATR/Chk1/2 kinase activities by specific inhibitors significantly abrogates up-regulation.
conclusionsThe present study provides evidence that regulation of the PVR/CD155 DNAM-1 ligand expression by nitric oxide may represent an additional immune-mediated mechanism and supports the anti-myeloma activity of nitric oxide donors.
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