ArticleCancer research2016
Heparanase 2 Attenuates Head and Neck Tumor Vascularity and Growth.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Heparanase 2 (Hpa2) protects the exocrine pancreas from damages of Western diet and pancreatic cancer.International journal of biological sciences · 2026Article
- Heparanase2 inhibits the growth of gallbladder cancer by regulating the VEGF/VEGFR pathway.Discover oncology · 2025Article
- Heparanase 2 Modulates Vascular Permeability via Heparan Sulfate-Dependent Growth Factor Signaling.Arteriosclerosis, thrombosis, and vascular biology · 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
- Current understanding of heparanase 2 regulation, a non-heparanase.Biochemical Society transactions · 2025Article
- Tumor- and host-derived heparanase-2 (Hpa2) attenuates tumorigenicity: role of Hpa2 in macrophage polarization and BRD7 nuclear localization.Cell death & disease · 2024Article
- Nuclear localization of heparanase 2 (Hpa2) attenuates breast carcinoma growth and metastasis.Cell death & disease · 2024Article
- Heparanase 2 (Hpa2)- a new player essential for pancreatic acinar cell differentiation.Cell death & disease · 2023Article
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- Heparanase 1 Upregulation Promotes Tumor Progression and Is a Predictor of Low Survival for Oral Cancer.Frontiers in cell and developmental biology · 2022Article
- Induction of heparanase 2 (Hpa2) expression by stress is mediated by ATF3.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- A Pro-Tumorigenic Effect of Heparanase 2 (Hpa2) in Thyroid Carcinoma Involves Its Localization to the Nuclear Membrane.Frontiers in oncology · 2021Article
- Elucidating the Consequences of Heparan Sulfate Binding by Heparanase 2.Frontiers in oncology · 2020Article
- Forty Years of Basic and Translational Heparanase Research.Advances in experimental medicine and biology · 2020Review
- Heparanase-2 protects from LPS-mediated endothelial injury by inhibiting TLR4 signalling.Scientific reports · 2019Article
- Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder.Kidney international · 2019Article
- Heparanase: A Challenging Cancer Drug Target.Frontiers in oncology · 2019Review
- Opposing Functions of Heparanase-1 and Heparanase-2 in Cancer Progression.Trends in biochemical sciences · 2018Review
- Activated HGF-c-Met Axis in Head and Neck Cancer.Cancers · 2017Review
- Extracellular matrix alterations in the Peyronie's disease.Journal of advanced research · 2017Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The endoglycosidase heparanase specifically cleaves the heparan sulfate (HS) side chains on proteoglycans, an activity that has been implicated strongly in tumor metastasis and angiogenesis. Heparanase-2 (Hpa2) is a close homolog of heparanase that lacks intrinsic HS-degrading activity but retains the capacity to bind HS with high affinity. In head and neck cancer patients, Hpa2 expression was markedly elevated, correlating with prolonged time to disease recurrence and inversely correlating with tumor cell dissemination to regional lymph nodes, suggesting that Hpa2 functions as a tumor suppressor. The molecular mechanism associated with favorable prognosis following Hpa2 induction is unclear. Here we provide evidence that Hpa2 overexpression in head and neck cancer cells markedly reduces tumor growth. Restrained tumor growth was associated with a prominent decrease in tumor vascularity (blood and lymph vessels), likely due to reduced Id1 expression, a transcription factor highly implicated in VEGF-A and VEGF-C gene regulation. We also noted that tumors produced by Hpa2-overexpressing cells are abundantly decorated with stromal cells and collagen deposition, correlating with a marked increase in lysyl oxidase expression. Notably, heparanase enzymatic activity was unimpaired in cells overexpressing Hpa2, suggesting that reduced tumor growth is not caused by heparanase regulation. Moreover, growth of tumor xenografts by Hpa2-overexpressing cells was unaffected by administration of a mAb that targets the heparin-binding domain of Hpa2, implying that Hpa2 function does not rely on heparanase or heparan sulfate. Cancer Res; 76(9); 2791-801. ©2016 AACR.
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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.