ArticleOncogene2014
Heparanase promotes lymphangiogenesis and tumor invasion in pancreatic neuroendocrine tumors.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- The Role of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Tumors.International journal of molecular sciences · 2025Review
- Curcumin protects extracellular matrix to maintain microenvironmental stability inhibiting colon cancer metastasis through HPSE/IL-6/STAT5 axis.Die Naturwissenschaften · 2025Article
- Characterization of the Pancreatic Neuroendocrine Neoplasm Immune Microenvironment.Cancer medicine · 2025Review
- Identification of a novel lymphangiogenesis signature associated with immune cell infiltration in colorectal cancer based on bioinformatics analysis.BMC medical genomics · 2024Article
- Models in Pancreatic Neuroendocrine Neoplasms: Current Perspectives and Future Directions.Cancers · 2023Review
- Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments.Molecular cancer · 2023Review
- PTEN regulates invasiveness in pancreatic neuroendocrine tumors through DUSP19-mediated VEGFR3 dephosphorylation.Journal of biomedical science · 2022Article
- Pancreatic Cancer Cell-Derived Exosomes Promote Lymphangiogenesis by Downregulating ABHD11-AS1 Expression.Cancers · 2022Article
- Article
- Heparanase 1 Upregulation Promotes Tumor Progression and Is a Predictor of Low Survival for Oral Cancer.Frontiers in cell and developmental biology · 2022Article
- 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
- Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020Review
- Review
- Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression.International journal of molecular sciences · 2020Review
- TAMing pancreatic cancer: combat with a double edged sword.Molecular cancer · 2019Review
- Immunomodulatory activities of pixatimod: emerging nonclinical and clinical data, and its potential utility in combination with PD-1 inhibitors.Journal for immunotherapy of cancer · 2018Article
- Knockdown of Heparanase Suppresses Invasion of Human Trophoblasts by Activating p38 MAPK Signaling Pathway.Disease markers · 2018Article
- The lymphatic system and pancreatic cancer.Cancer letters · 2016Review
- Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression.Oncotarget · 2016Article
- Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response.Nature reviews. Cancer · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Heparan sulfate proteoglycans are an important and abundant component of the extracellular matrix, which undergo substantial remodeling throughout tumorigenesis via the enzymatic activity of heparanase. Heparanase has been shown to be upregulated in many human cancers; however, its specific functions in human pancreatic neuroendocrine tumors (PanNETs) and spontaneous mouse models of cancer have not been evaluated. Here, we investigated the role of heparanase in PanNETs using patient samples and the RIP1-Tag2 (RT2) PanNET-transgenic mouse model. High heparanase expression significantly correlated with more advanced tumor stage, higher tumor grade and the presence of distant metastasis in PanNET patients. We genetically manipulated heparanase levels in the RT2 model using heparanase-transgenic mice, which constitutively overexpress heparanase, and heparanase-knockout mice. Heparanase was found to have a critical role in promoting tumor invasion, through both macrophage and cancer cell sources in the tumor microenvironment. In addition, elevated heparanase levels significantly increased peritumoral lymphangiogenesis in vivo and promoted the trans-differentiation of macrophages into lymphatic endothelial cell-like structures in culture. Conversely, we found that heparanase deletion led to increased angiogenesis and pericyte coverage. Together, these data identify important roles for heparanase in regulating several critical aspects of tumorigenesis, demonstrating that heparanase represents a potential therapeutic target for PanNET patients.
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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.