ArticleOncogene2015
A novel cysteine cathepsin inhibitor yields macrophage cell death and mammary tumor regression.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Monocyte-Macrophage Lineages in Cancer: Biology, Plasticity, and Therapeutic Targeting.Cancer biome and targeted therapy · 2026Article
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Tumor-Associated Macrophage in Breast Tumor Microenvironment.International journal of molecular sciences · 2025Review
- ACOD1-mediated lysosomal membrane permeabilization contributes toProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Structural Elucidation and Antiviral Activity of Covalent Cathepsin L Inhibitors.Journal of medicinal chemistry · 2024Article
- Ruthenium-Cathepsin Inhibitor Conjugates for Green Light-Activated Photodynamic Therapy and Photochemotherapy.Inorganic chemistry · 2024Article
- Article
- The emerging roles of metabolism in the crosstalk between breast cancer cells and tumor-associated macrophages.International journal of biological sciences · 2023Review
- Wound Healing versus Metastasis: Role of Oxidative Stress.Biomedicines · 2022Review
- Infiltration of Apoptotic M2 Macrophage Subpopulation Is Negatively Correlated with the Immunotherapy Response in Colorectal Cancer.International journal of molecular sciences · 2022Article
- Helicobacter pylori and gastric cancer: a lysosomal protease perspective.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Review
- Improved Cathepsin Probes for Sensitive Molecular Imaging.Molecules (Basel, Switzerland) · 2022Article
- Spatial transcriptomics of the lacrimal gland features macrophage activity and epithelium metabolism as key alterations during chronic inflammation.Frontiers in immunology · 2022Article
- Immune cell - produced ROS and their impact on tumor growth and metastasis.Redox biology · 2021Review
- Dual-Mechanism Quenched Fluorogenic Probe Provides Selective and Rapid Detection of Cathepsin L Activity*.ChemMedChem · 2021Article
- Macrophage-Regulatory T Cell Interactions Promote Type 2 Immune Homeostasis Through Resistin-Like Molecule α.Frontiers in immunology · 2021Article
- The Role of Cysteine Peptidases in Hematopoietic Stem Cell Differentiation and Modulation of Immune System Function.Frontiers in immunology · 2021Review
- Cathepsins B, D, and G Are Expressed in Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although cysteine cathepsins have been identified as key regulators of cancer growth, their specific role in tumor development remains unclear. Recent studies have shown that high activity levels of tumor cathepsins are primarily a result of increased cathepsin activity in cancer-promoting tumor-associated macrophages (TAMs). To further investigate the role of cysteine cathepsin activity in normal and polarized macrophages, we established in vitro and in vivo models of macrophage differentiation and polarization and used a novel cysteine cathepsin inhibitor, GB111-NH2, to block the activity of cathepsins B, L and S. Here we show that in vitro, cysteine cathepsin inhibition yields both apoptosis and proliferation of macrophages, owing to increased oxidative stress. Proteomic analysis of cathepsin- inhibited macrophages demonstrates inhibition of autophagy, suggesting a likely cause of elevated reactive oxygen species (ROS) levels. In vivo models of mammary cancer further show that cathepsin inhibition yields TAM death owing to increased ROS levels. Strikingly, apoptosis in TAMs yields a seemingly cell non-autonomous death of neighboring cancer cells, and regression of the primary growth. These results show that cysteine cathepsin inhibitors can specifically trigger macrophage cell death and may function as an effective anticancer therapy in tumors with high levels of TAMs.
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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.