ArticleProceedings of the National Academy of Sciences of the United States of America2016
Heparanase is required for activation and function of macrophages.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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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.
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Who cites it
61 citing papers in PubMed, 102 citations in OpenAlex.
- Maturation-Dependent Constraints in the Ability of Human Monocytes to Initiate Trained Immunity.MedComm · 2026Article
- Heparanase, Endothelial Dysfunction, and Cardiovascular Risk: The Emerging Role of Vitamin D.ACS pharmacology & translational science · 2026Review
- An integral membrane constitutively active heparanase enhances the tumor infiltration capability of NK cells.Oncoimmunology · 2025Article
- Heparan sulfate as a central modulator of growth factor dynamics in tissue regeneration.APL bioengineering · 2025Article
- The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue-Specific Perspectives.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Tumor- and host-derived heparanase-2 (Hpa2) attenuates tumorigenicity: role of Hpa2 in macrophage polarization and BRD7 nuclear localization.Cell death & disease · 2024Article
- Heparanase-induced endothelial glycocalyx degradation exacerbates lung ischemia/reperfusion injury in male mice.Physiological reports · 2024Article
- Design Principle of Heparanase Inhibitors: A Combined In Vitro and In Silico Study.ACS medicinal chemistry letters · 2024Article
- Review
- The Uptake of Heparanase into Mast Cells Is Regulated by Its Enzymatic Activity to Degrade Heparan Sulfate.International journal of molecular sciences · 2024Article
- Discovery and development of small-molecule heparanase inhibitors.Bioorganic & medicinal chemistry · 2023Review
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- Investigating the Role of Heparanase in Breast Cancer Development Utilising the MMTV-PyMT Murine Model of Mammary Carcinoma.Cancers · 2023Article
- Heparanase Modulates Chromatin Accessibility.Cells · 2023Article
- Role of heparanase in pulmonary hypertension.Frontiers in pharmacology · 2023Review
- Role of heparanase in ARDS through autophagy and exosome pathway (review).Frontiers in pharmacology · 2023Review
- Review
- Review
- Macrophages Upregulate Estrogen Receptor Expression in the Model of Obesity-Associated Breast Carcinoma.Cells · 2022Article
- Synthesis of Novel Glycolipid Mimetics of Heparan Sulfate and Their Application in Colorectal Cancer Treatment in a Mouse Model.Chemistry, an Asian journal · 2022Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emerging role of heparanase in tumor initiation, growth, metastasis, and chemoresistance is well recognized and is encouraging the development of heparanase inhibitors as anticancer drugs. Unlike the function of heparanase in cancer cells, very little attention has been given to heparanase contributed by cells composing the tumor microenvironment. Here we used a genetic approach and examined the behavior and function of macrophages isolated from wild-type (WT) and heparanase-knockout (Hpa-KO) mice. Hpa-KO macrophages express lower levels of cytokines (e.g., TNFα, IL1-β) and exhibit lower motility and phagocytic capacities. Intriguingly, inoculation of control monocytes together with Lewis lung carcinoma (LLC) cells into Hpa-KO mice resulted in nearly complete inhibition of tumor growth. In striking contrast, inoculating LLC cells together with monocytes isolated from Hpa-KO mice did not affect tumor growth, indicating that heparanase is critically required for activation and function of macrophages. Mechanistically, we describe a linear cascade by which heparanase activates Erk, p38, and JNK signaling in macrophages, leading to increased c-Fos levels and induction of cytokine expression in a manner that apparently does not require heparanase enzymatic activity. These results identify heparanase as a key mediator of macrophage activation and function in tumorigenesis and cross-talk with the tumor microenvironment.
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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.