ArticleOncotarget2015
Cysteine cathepsin activity suppresses osteoclastogenesis of myeloid-derived suppressor cells in breast cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- C/EBPβ dictates postmenopausal FSHβ transcription and blockade of AEP/C/EBPβ pathway alleviates osteoporosis.Bone research · 2026Article
- The Role of Extracellular Proteases and Extracellular Matrix Remodeling in the Pre-Metastatic Niche.Biomolecules · 2025Review
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Coxiella burnetii manipulates the lysosomal protease cathepsin B to facilitate intracellular success.Nature communications · 2025Article
- PKM2 orchestrates tumor progression via metabolic reprogramming and MDSCs-mediated immune suppression in the tumor microenvironment.Frontiers in immunology · 2025Review
- Innate Immunity and Synovitis: Key Players in Osteoarthritis Progression.International journal of molecular sciences · 2024Review
- Disturbed intracellular folate homeostasis impairs autophagic flux and increases hepatocytic lipid accumulation.BMC biology · 2024Article
- Cathepsin X deficiency alters the processing and localisation of cathepsin L and impairs cleavage of a nuclear cathepsin L substrate.Biological chemistry · 2024Article
- In vitro osteoclastogenesis assessment using murine myeloid-derived suppressor cells.Methods in cell biology · 2024Article
- The Role of Cysteine Protease Cathepsins B, H, C, and X/Z in Neurodegenerative Diseases and Cancer.International journal of molecular sciences · 2023Review
- Chemical Tools to Image the Activity of PAR-Cleaving Proteases.ACS bio & med chem Au · 2023Review
- Cysteine Cathepsins in Breast Cancer: Promising Targets for Fluorescence-Guided Surgery.Molecular imaging and biology · 2023Review
- The role of lysosomal peptidases in glioma immune escape: underlying mechanisms and therapeutic strategies.Frontiers in immunology · 2023Review
- The Mammalian Cysteine Protease Legumain in Health and Disease.International journal of molecular sciences · 2022Review
- Bone Microenvironment-Suppressed T Cells Increase Osteoclast Formation and Osteolytic Bone Metastases in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Cathepsin X Activity Does Not Affect NK-Target Cell Synapse but Is Rather Distributed to Cytotoxic Granules.International journal of molecular sciences · 2021Article
- Beyond immunosuppressive effects: dual roles of myeloid-derived suppressor cells in bone-related diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Age-related expansion and increased osteoclastogenic potential of myeloid-derived suppressor cells.Molecular immunology · 2021Article
- Legumain Induces Oral Cancer Pain by Biased Agonism of Protease-Activated Receptor-2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.Frontiers in molecular biosciences · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cysteine cathepsin proteases contribute to many normal cellular functions, and their aberrant activity within various cell types can contribute to many diseases, including breast cancer. It is now well accepted that cathepsin proteases have numerous cell-specific functions within the tumor microenvironment that function to promote tumor growth and invasion, such that they may be valid targets for anti-metastatic therapeutic approaches. Using activity-based probes, we have examined the activity and expression of cysteine cathepsins in a mouse model of breast cancer metastasis to bone. In mice bearing highly metastatic tumors, we detected abundant cysteine cathepsin expression and activity in myeloid-derived suppressor cells (MDSCs). These immature immune cells have known metastasis-promoting roles, including immunosuppression and osteoclastogenesis, and we assessed the contribution of cysteine cathepsins to these functions. Blocking cysteine cathepsin activity with multiple small-molecule inhibitors resulted in enhanced differentiation of multinucleated osteoclasts. This highlights a potential role for cysteine cathepsin activity in suppressing the fusion of osteoclast precursor cells. In support of this hypothesis, we found that expression and activity of key cysteine cathepsins were downregulated during MDSC-osteoclast differentiation. Another cysteine protease, legumain, also inhibits osteoclastogenesis, in part through modulation of cathepsin L activity. Together, these data suggest that cysteine protease inhibition is associated with enhanced osteoclastogenesis, a process that has been implicated in bone metastasis.
Indexed as
Identifiers
What OpenQuestion holds
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.