ArticleOncotarget2017
Intratumoral acidosis fosters cancer-induced bone pain through the activation of the mesenchymal tumor-associated stroma in bone metastasis from breast carcinoma.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Modeling and targeting the hostile physicochemical niche in bone metastasis: from experimental platforms to niche-directed therapy.Frontiers in cell and developmental biology · 2026Review
- Mesenchymal stroma drives axonogenesis and nerve-induced aggressiveness in osteosarcoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Primary Bone Tumors and Breast Cancer-Induced Bone Metastases: In Vivo Animal Models and New Alternative Approaches.Biomedicines · 2024Review
- Mesenchymal stem cell transplantation plays a role in relieving cancer pain.Frontiers in pharmacology · 2024Review
- Vacuolar ATPase Is a Possible Therapeutic Target in Acute Myeloid Leukemia: Focus on Patient Heterogeneity and Treatment Toxicity.Journal of clinical medicine · 2023Article
- Self-assembled innervated vasculature-on-a-chip to study nociception.Biofabrication · 2023Article
- The Prognostic Value of the Serum Level of C-Reactive Protein for Survival of Children with Ewing's Sarcoma.Cancers · 2023Article
- Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases.Biomedicines · 2022Article
- Transcriptomic Response to Acidosis Reveals Its Contribution to Bone Metastasis in Breast Cancer Cells.Cells · 2022Article
- Dietary Acid Load, Serum Polychlorinated Biphenyl Levels, and Mortality Following Breast Cancer in the Long Island Breast Cancer Study Project.International journal of environmental research and public health · 2021Article
- Article
- Acid Microenvironment in Bone Sarcomas.Cancers · 2021Review
- Metastasis-associated fibroblasts: an emerging target for metastatic cancer.Biomarker research · 2021Review
- Acid-Induced Inflammatory Cytokines in Osteoblasts: A Guided Path to Osteolysis in Bone Metastasis.Frontiers in cell and developmental biology · 2021Article
- Alterations in the CaExploration of targeted anti-tumor therapy · 2021Article
- Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New HInternational journal of molecular sciences · 2020Review
- Emergence of Cancer-Associated Fibroblasts as an Indispensable Cellular Player in Bone Metastasis Process.Cancers · 2020Review
- Switching Homes: How Cancer Moves to Bone.International journal of molecular sciences · 2020Review
- Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways.Immunology · 2020Review
- A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer Based upon Its Hydrogen Ion Dynamics.International journal of molecular sciences · 2020Review
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-induced bone pain (CIBP) is common in patients with bone metastases (BM), significantly impairing quality of life. The current treatments for CIBP are limited since they are often ineffective. Local acidosis derived from glycolytic carcinoma and tumor-induced osteolysis is only barely explored cause of pain. We found that breast carcinoma cells that prefer bone as a metastatic site have very high extracellular proton efflux and expression of pumps/ion transporters associated with acid-base balance (MCT4, CA9, and V-ATPase). Further, the impairment of intratumoral acidification via V-ATPase targeting in xenografts with BM significantly reduced CIBP, as measured by incapacitance test. We hypothesize that in addition to the direct acid-induced stimulation of nociceptors in the bone, a novel mechanism mediated by the acid-induced and tumor-associated mesenchymal stroma might ultimately lead to nociceptor sensitization and hyperalgesia. Consistent with this, short-term exposure of cancer-associated fibroblasts, mesenchymal stem cells, and osteoblasts to pH 6.8 promotes the expression of inflammatory and nociceptive mediators (NGF, BDNF, IL6, IL8, IL1b and CCL5). This is also consistent with a significant correlation between breakthrough pain, measured by pain questionnaire, and combined high serum levels of BDNF and IL6 in patients with BM, and also by immunofluorescence staining showing IL8 expression that was more in mesenchymal stromal cells rather than in tumors cells, and close to LAMP-2 positive acidifying carcinoma cells in BM tissue sections. In summary, intratumoral acidification in BM might promote CIBP also by activating the tumor-associated stroma, offering a new target for palliative treatments in advanced cancer.
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