ArticleCancer research2020
Heparanase and Chemotherapy Synergize to Drive Macrophage Activation and Enhance Tumor Growth.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Heparan Sulfate Proteoglycans in Immunity.Proteoglycan research · 2026Article
- 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
- Review
- H3K4 trimethylation regulates cancer immunity: a promising therapeutic target in combination with immunotherapy.Journal for immunotherapy of cancer · 2023Review
- Ubiquitin-proteasome system as a target for anticancer treatment-an update.Archives of pharmacal research · 2023Review
- Heparin Mimetics and Their Impact on Extracellular Matrix Protein Assemblies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Heparanase Modulates Chromatin Accessibility.Cells · 2023Article
- Heparanase is the possible link between monkeypox and Covid-19: robust candidature in the mystic and present perspective.AMB Express · 2023Review
- Non-enzymatic heparanase enhances gastric tumor proliferation via TFEB-dependent autophagy.Oncogenesis · 2022Article
- Role of macrophages in tumor progression and therapy (Review).International journal of oncology · 2022Review
- Targeting the Tumor Microenvironment: A Close Up of Tumor-Associated Macrophages and Neutrophils.Frontiers in oncology · 2022Review
- Induction of heparanase 2 (Hpa2) expression by stress is mediated by ATF3.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Extracellular matrix guidance of autophagy: a mechanism regulating cancer growth.Open biology · 2022Review
- Upregulation of ERK-EGR1-heparanase axis by HDAC inhibitors provides targets for rational therapeutic intervention in synovial sarcoma.Journal of experimental & clinical cancer research : CR · 2021Article
- Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design.Pharmaceutics · 2021Review
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- Article
- Impact of Adjuvant Treatment on Heparanase Concentration in Invasive, Unilateral Breast Cancer Patients: Results of a Prospective Single-Centre Cohort Study.Journal of clinical medicine · 2021Article
- Biology of the Heparanase-Heparan Sulfate Axis and Its Role in Disease Pathogenesis.Seminars in thrombosis and hemostasis · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
The emerging role of heparanase in tumor initiation, growth, metastasis, and chemoresistance is well recognized, encouraging the development of heparanase inhibitors as anticancer drugs. Unlike the function of heparanase in cancer cells, little attention has been given to heparanase contributed by cells composing the tumor microenvironment. Here, we focused on the cross-talk between macrophages, chemotherapy, and heparanase and the combined effect on tumor progression. Macrophages were markedly activated by chemotherapeutics paclitaxel and cisplatin, evidenced by increased expression of proinflammatory cytokines, supporting recent studies indicating that chemotherapy may promote rather than suppress tumor regrowth and spread. Strikingly, cytokine induction by chemotherapy was not observed in macrophages isolated from heparanase-knockout mice, suggesting macrophage activation by chemotherapy is heparanase dependent. paclitaxel-treated macrophages enhanced the growth of Lewis lung carcinoma tumors that was attenuated by a CXCR2 inhibitor. Mechanistically, paclitaxel and cisplatin activated methylation of histone H3 on lysine 4 (H3K4) in wild-type but not in heparanase-knockout macrophages. Furthermore, the H3K4 presenter WDR5 functioned as a molecular determinant that mediated cytokine induction by paclitaxel. This epigenetic, heparanase-dependent host-response mechanism adds a new perspective to the tumor-promoting functions of chemotherapy, and offers new treatment modalities to optimize chemotherapeutics. SIGNIFICANCE: Chemotherapy-treated macrophages are activated to produce proinflammatory cytokines, which are blunted in the absence of heparanase.
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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.