ArticleCancer research2011
Targeting hyaluronidase for cancer therapy: antitumor activity of sulfated hyaluronic acid in prostate cancer cells.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 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
72 citing papers in PubMed, 152 citations in OpenAlex.
- Article
- Molecular weight regulation strategies in microbial synthesis of hyaluronic acid: current status and future perspectives.World journal of microbiology & biotechnology · 2025Review
- HMMR in human cancers: regulatory mechanism and biological function.Journal of translational medicine · 2025Review
- Polymeric nanocarriers in drug delivery, bioimaging, and biosensing: advances and perspectives on nanomicelles, nanogels, and dendrimers.RSC advances · 2025Review
- Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025Review
- Extracellular matrix: unlocking new avenues in cancer treatment.Biomarker research · 2025Review
- Characterization of a NaWorld journal of microbiology & biotechnology · 2025Article
- Sustainable and biocompatible hybrid materials-based sulfated polysaccharides for biomedical applications: a review.RSC advances · 2025Review
- Inducible engineering precursor metabolic flux for synthesizing hyaluronic acid of customized molecular weight in Streptococcus zooepidemicus.Microbial cell factories · 2025Article
- Targeting glioblastoma tumor hyaluronan to enhance therapeutic interventions that regulate metabolic cell properties.Advanced therapeutics · 2024Article
- Mendelian randomization reveals potential causal relationships between cellular senescence-related genes and multiple cancer risks.Communications biology · 2024Article
- The Anticancer Activities of Natural Terpenoids That Inhibit Both Melanoma and Non-Melanoma Skin Cancers.International journal of molecular sciences · 2024Review
- A pH‑responsive hyaluronic acid nano‑vehicle co‑encapsulating doxorubicin and all‑trans retinoic acid for the inhibition of hepatic stellate cell‑induced tumor growth and metastasis.Molecular medicine reports · 2023Article
- Multidirectional Effects of Terpenoids fromPharmaceuticals (Basel, Switzerland) · 2023Article
- Research Progress in Enzymatically Cross-Linked Hydrogels as Injectable Systems for Bioprinting and Tissue Engineering.Gels (Basel, Switzerland) · 2023Review
- The role of hyaluronan in renal cell carcinoma.Frontiers in immunology · 2023Review
- Cancer immune exclusion: breaking the barricade for a successful immunotherapy.Frontiers in oncology · 2023Review
- Hyaluronic Acid as a Modern Approach in Anticancer Therapy-Review.International journal of molecular sciences · 2022Review
- Ovarian Cancer-Cell Pericellular Hyaluronan Deposition Negatively Impacts Prognosis of Ovarian Cancer Patients.Biomedicines · 2022Article
- Multiple Cell Cultures for MRI Analysis.International journal of molecular sciences · 2022Review
12 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
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The tumor cell-derived hyaluronidase (HAase) HYAL-1 degrades hyaluronic acid (HA) into proangiogenic fragments that support tumor progression. Although HYAL-1 is a critical determinant of tumor progression and a marker for cancer diagnosis and metastasis prediction, it has not been evaluated as a target for cancer therapy. Similarly, sulfated hyaluronic acid (sHA) has not been evaluated for biological activity, although it is an HAase inhibitor. In this study, we show that sHA is a potent inhibitor of prostate cancer. sHA blocked the proliferation, motility, and invasion of LNCaP, LNCaP-AI, DU145, and LAPC-4 prostate cancer cells, and induced caspase-8-dependent apoptosis associated with downregulation of Bcl-2 and phospho-Bad. sHA inhibited Akt signaling including androgen receptor (AR) phosphorylation, AR activity, nuclear factor κB (NFκB) activation, and VEGF expression. These effects were traced to a blockade in complex formation between phosphoinositide 3-kinase (PI3K) and HA receptors and to a transcriptional downregulation of HA receptors, CD44, and RHAMM, along with PI3K inhibition. Angiogenic HA fragments or overexpression of myristoylated Akt or HA receptors blunted these effects of sHA, implicating a feedback loop between HA receptors and PI3K/Akt signaling in the mechanism of action. In an animal model, sHA strongly inhibited LNCaP-AI prostate tumor growth without causing weight loss or apparent serum-organ toxicity. Inhibition of tumor growth was accompanied by a significant decrease in tumor angiogenesis and an increase in apoptosis index. Taken together, our findings offer mechanistic insights into the tumor-associated HA-HAase system and a preclinical proof-of-concept of the safety and efficacy of sHA to control prostate cancer growth and progression.
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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.