ArticleCancer research2014
Heparanase cooperates with Ras to drive breast and skin tumorigenesis.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 71 citations in OpenAlex.
- Heparan Sulfate Proteoglycans (HSPGs) and Their Degradation in Health and Disease.Biomolecules · 2025Review
- Nuclear localization of heparanase 2 (Hpa2) attenuates breast carcinoma growth and metastasis.Cell death & disease · 2024Article
- miR-184 represses β-catenin and behaves as a skin tumor suppressor.Cell death & disease · 2024Article
- Extracellular matrix in skin diseases: The road to new therapies.Journal of advanced research · 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
- 4-O-Substituted Glucuronic Cyclophellitols are Selective Mechanism-Based Heparanase Inhibitors.ChemMedChem · 2023Article
- Review
- Phase Ib open-label, multicenter study of pixatimod, an activator of TLR9, in combination with nivolumab in subjects with microsatellite-stable metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma and other solid tumors.Journal for immunotherapy of cancer · 2023Article
- Non-enzymatic heparanase enhances gastric tumor proliferation via TFEB-dependent autophagy.Oncogenesis · 2022Article
- Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction.ACS central science · 2022Article
- Role of heparinase in the gastrointestinal dysfunction of sepsis (Review).Experimental and therapeutic medicine · 2022Review
- Heparanase regulates EMT and cancer stem cell properties in prostate tumors.Frontiers in oncology · 2022Article
- Nano drug delivery systems improve metastatic breast cancer therapy.Medical review (2021) · 2021Article
- Article
- Article
- Novel Therapeutic Targets and Immune Dysfunction in Malignant Pleural Mesothelioma.Frontiers in pharmacology · 2021Review
- Heparanase, cell signaling, and viral infections.Cellular and molecular life sciences : CMLS · 2020Review
- Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020Review
- Significance of host heparanase in promoting tumor growth and metastasis.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
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 4 institutions in 3 countries.
Funding
Abstract
Heparanase has been implicated in cancer but its contribution to the early stages of cancer development is uncertain. In this study, we utilized nontransformed human MCF10A mammary epithelial cells and two genetic mouse models [Hpa-transgenic (Hpa-Tg) and knockout mice] to explore heparanase function at early stages of tumor development. Heparanase overexpression resulted in significantly enlarged asymmetrical acinar structures, indicating increased cell proliferation and decreased organization. This phenotype was enhanced by coexpression of heparanase variants with a mutant H-Ras gene, which was sufficient to enable growth of invasive carcinoma in vivo. These observations were extended in vivo by comparing the response of Hpa-Tg mice to a classical two-stage 12-dimethylbenz(a)anthracene (DMBA)/12-o-tetradecanoylphorbol-13-acetate (TPA) protocol for skin carcinogenesis. Hpa-Tg mice overexpressing heparanase were far more sensitive than control mice to DMBA/TPA treatment, exhibiting a 10-fold increase in the number and size of tumor lesions. Conversely, DMBA/TPA-induced tumor formation was greatly attenuated in Hpa-KO mice lacking heparanase, pointing to a critical role of heparanase in skin tumorigenesis. In support of these observations, the heparanase inhibitor PG545 potently suppressed tumor progression in this model system. Taken together, our findings establish that heparanase exerts protumorigenic properties at early stages of tumor initiation, cooperating with Ras to dramatically promote malignant development.
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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.