Hyaluronan: Towards novel anti-cancer therapeutics

Karbownik, Michał Seweryn; Nowak, Jerzy Z.

doi:10.1016/s1734-1140(13)71465-8

Cited by 119 publications

(107 citation statements)

References 130 publications

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“…Unlike the carbohydrate moiety of glycoproteins, the glycosaminoglycan hyaluronic acid is a freely occurring, high-molecular-weight polysaccharide found in the extracellular matrix (Comper 1996). Not only is hyaluronic acid a structural component of the matrix, but it is also a signaling molecule that is directly recognized by several receptors, including CD44, RHAMM, and Toll-like receptors (Aruffo et al 1990;Schaefer 2010;Karbownik and Nowak 2013). For example, binding of hyaluronic acid to the CD44 receptor activates the NLRP3 inflammasome, leading to secretion of interleukin-1b (IL-1b) (Yamasaki et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase

2014

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We report that the Bacillus subtilis exopolysaccharide (EPS) is a signaling molecule that controls its own production. EPS synthesis depends on a tyrosine kinase that consists of a membrane component (EpsA) and a kinase component (EpsB). EPS interacts with the extracellular domain of EpsA, which is a receptor, to control kinase activity. In the absence of EPS, the kinase is inactivated by autophosphorylation. The presence of EPS inhibits autophosphorylation and instead promotes the phosphorylation of a glycosyltransferase in the biosynthetic pathway, thereby stimulating the production of EPS. Thus, EPS production is subject to a positive feedback loop that ties its synthesis to its own concentration. Tyrosine kinase-mediated self-regulation could be a widespread feature of the control of exopolysaccharide production in bacteria.

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Section: Discussionmentioning

confidence: 99%

Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase

2014

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“…To observe genetic differences in AGL low bladder cancer, a transcriptional profiling of human bladder cancer cells with and without AGL expression was performed, searching for genes differentially regulated with loss of AGL (15). Hyaluronic acid synthase 2 (HAS2), a gene associated with HA synthesis (16,17), was one of the overexpressed genes with AGL loss (15). Elevated HAS2 expression is correlated with high-grade bladder cancer and poor patient mortality, making HAS2 a gene of interest for further study in the AGL model of bladder cancer (15).…”

Section: Agl and Hyaluronic Acid Synthesismentioning

confidence: 99%

“…Known as non-branching glycosaminoglycans, HA vary in size based on the number of disaccharide repeats, with glucose serving as the precursor molecule for HA synthesis (16,17). Located in the extracellular matrix, HA can bind to cell surface receptors designed for different sized HA (18).…”

Section: Agl and Hyaluronic Acid Synthesismentioning

confidence: 99%

“…Located in the extracellular matrix, HA can bind to cell surface receptors designed for different sized HA (18). HA is biologically relevant in angiogenesis, anchorage independent growth and for allowing cell-to-cell interactions with cancer tissue and surrounding stromal tissue (16,19). The significance of HA in cancer biology provided a reason to further investigate HAS2-mediated HA synthesis in AGL low bladder cancer.…”

Section: Agl and Hyaluronic Acid Synthesismentioning

confidence: 99%

“…Hyaladherins, or proteins that bind to extracellular HA, can be either cell surface receptors or extracellular matrix proteins (21). Two of these cell surface hyaladherins, RHAMM and CD44, are clinically significant in various cancer models (16,19,22). These hyaladherins have been demonstrated to provide multi-drug resistance, assist with anchorage independent growth, and cell motility of cancer cells (23)(24)(25).…”

Section: Agl and Hyaluronic Acid Receptorsmentioning

confidence: 99%

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Involvement of glycogen debranching enzyme in bladder cancer

Weinhaus

Guin

2017

Biomedical Reports

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Abstract. Bladder cancer is the most common malignancy of the urinary system, however the molecular pathways underlying this disease are incompletely understood. To understand new regulators of bladder cancer progression, the authors carried out a functional genomic screen which identified glycogen debranching enzyme (AGL) as a novel regulator of bladder cancer growth. Glycogen debranching enzyme is involved in glycogen breakdown and germline loss of function mutation of this gene leads to glycogen storage disease type III. To the best of the authors' knowledge, the present study is the first to demonstrate that loss of AGL leads to aggressive bladder tumor growth. AGL mRNA and protein expression in bladder tumors serve as a prognostic marker for patients. Interestingly, AGL's participation in regulating tumor growth is independent of its enzymatic function and involvement with glycogen metabolism in general. Detailed metabolomics and transcriptomic analysis indicated that increases in glucose metabolism, glycine synthesis driven by serine hydroxymethyltransferase 2 and increases in hyaluronic acid synthase 2-driven HA synthesis are major contributors of aggressive bladder tumor growth with loss of AGL. However, the detailed mechanism of how AGL regulates the above mentioned metabolic and genetic pathways is unknown and is being investigated. The present review focuses on AGL's involvement in bladder cancer.

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Characterization and Biomedical Application Opportunities of the Nanoparticle's Protein Corona

Jiang

2022

Adv Materials Inter

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with all three external dimensions in the nanoscale, whose longest and shortest axes do not differ significantly, with a significant difference typically being a factor of at least 3." This size allows nanoscale materials to be integrated into biomedical equipment since most biological systems are also nanoscale. [2] In addition to the definition of size, NPs used in biomedical research have a high degree of diversity in structure, chemical composition, morphology, hydrophobicity, surface chemistry, electrostatic charge, and other properties. Figure 1 shows several typical NPs (magnetic NPs, carbon nanotubes, liposomes, micelles, etc.) and the related phenomena in biomedicine. [3][4][5][6][7] Various nanotechnology platforms based on these NPs have been well developed. [8][9][10][11][12] The first-generation nanocarriers, e.g., polymeric NPs, polyethylene glycol (PEG)-modified liposomes, can improve the pharmacokinetics and tolerability of nanoformulated drugs. [13,14] Magnetic materials are attractive for applications in biomedicine, such as directly focusing the nanocarriers on the target area by an external magnetic field [15][16][17] or killing the cancerous cells through magnetically induced hyperthermia. [18,19] Moreover, the drugs for central nervous system diseases must cross the blood-brain barrier. The nanocarriers can specifically deliver the payloads to affected regions and accumulate in selected tissues, [20][21][22] assisting in solubilizing the compounds with low solubility (e.g., paclitaxel and atovaquone) [23] and protecting the molecules of proteins and/or nucleic acids from enzymatic degradation. The next-generation nanocarriers take advantage of active targeting methods to ensure drug delivery to specific areas. These strategies depend on the surface functionalization of nanocarriers with active targeting molecules, [24] for example, hyaluronic acid, [25] folic acid, [26] antibodies, [27] or aptamers. [28] For example, Chan and collaborators developed the DNA-assembled gold nanorod "core-satellite" structures for programmable drug loading and controllable release. [29] Moreover, researchers explored the functionality of DNA-assembled inorganic NPs for operating in the complicated biological systems. It was revealed that altering the targeting ligands on the surface increased the targeting efficiency by 2.5 times. [30] Therefore, NPs have a strong potential to increase the stability and solubility of the encapsulated drugs, and promote drug transport across membranes, as well as prolong the drug circulation times and halflife to improve the safety and efficacy of drugs. [31,32] Nanoparticles (NPs) are widely used in a variety of biomedical fields, such as drug delivery systems, novel theragnostic strategies, bioimaging, and biosensing. The protein corona formed by the contact between NPs and biological liquids changes the physicochemical nanoparticle characteristics, including size, shape, and surface statement. Moreover, it affects the biological fate of NPs in organisms, for instance, pharmac...

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Hyaluronan: Towards novel anti-cancer therapeutics

Cited by 119 publications

References 130 publications

Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase

Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase

Involvement of glycogen debranching enzyme in bladder cancer

Characterization and Biomedical Application Opportunities of the Nanoparticle's Protein Corona

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