Size Matters: Molecular Weight Specificity of Hyaluronan Effects in Cell Biology

Cyphert, Jaime M.; Trempus, Carol S.; Garantziotis, Stavros

doi:10.1155/2015/563818

Cited by 334 publications

(353 citation statements)

References 93 publications

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“…HYAL 2 is anchored on the external side of the cell surface: here it cleaves into oligosaccharides (oHA; approximately 25 disaccharide units, 2 x 10 4 Da) the extracellular HMW¬ HA (≥ 10 6 Da), which is linked to its receptor cluster of differentiation-44 (CD44). These intermediate fragments are internalized, transported first to endosomes and then to lysosomes, where they are degraded into tetrasaccharide units (800 Da) by HYAL 1 [51]. Differently from HYAL-1 and HYAL 2, PH20/SPAM1 shows not only endoglycosidase activity both at acidic and neutral pH, but also a role in fertilization [108].…”

Section: Ha Degradation In Human Bodymentioning

confidence: 99%

“…Molecular mass and circumstances of synthesis/degradation are the key factors defining HA biological actions [50,51,100]. Indeed, high molecular weight (HMW) and low molecular weight (LMW) hyaluronan can even display opposite effects [51,60], and when they are simultaneously present in a specific tissue, they can exert actions different from the simple sum of those of their separate size-related effects [51]. Extracellular HMW HA (≥ 10 6 Da) is anti-angiogenic, as it is able to inhibit endothelial cell growth [51,60,114].…”

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

“…Indeed, high molecular weight (HMW) and low molecular weight (LMW) hyaluronan can even display opposite effects [51,60], and when they are simultaneously present in a specific tissue, they can exert actions different from the simple sum of those of their separate size-related effects [51]. Extracellular HMW HA (≥ 10 6 Da) is anti-angiogenic, as it is able to inhibit endothelial cell growth [51,60,114]. Additionally, due its viscoelasticity, it acts as lubricating agent in the synovial joint fluid, thus protecting the articular cartilage [115].…”

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

“…During some environmental and pathological conditions -such as asthma, pulmonary fibrosis and hypertension, chronic obstructive pulmonary disease and rheumatoid arthritis-, HMW HA is cleaved into LMW HA (2 x 10 4 -10 6 Da), which has been shown to possess pro-inflammatory and pro-angiogenic activities [51,100]. Indeed, LMW hyaluronan is able to stimulate the production of proinflammatory cytokines, chemokines and growth factors [51], and to promote ECM remodeling [50].…”

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

“…Indeed, LMW hyaluronan is able to stimulate the production of proinflammatory cytokines, chemokines and growth factors [51], and to promote ECM remodeling [50]. Moreover, LMW HA can also induce tumor progression, exerting its influence on cell [51,116] and provoking ECM remodeling.…”

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

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Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Fallacara¹,

Baldini²,

Manfredini³

et al. 2018

Preprint

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Since its first isolation in 1934, hyaluronic acid (HA) has been studied across a variety of research areas. This unbranched glycosaminoglycan consisting of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid is almost ubiquitary in humans and in other vertebrates. HA is involved in many key processes -including cell signaling, wound reparation, tissue regeneration, morphogenesis, matrix organization and pathobiology-, and has unique physico-chemical properties -such as biocompatibility, biodegradability, mucoadhesivity, hygroscopicity and viscoelasticity. For these reasons, exogenous HA has been investigated as drug delivery system and treatment in cancer, ophthalmology, arthrology, pneumology, rhinology, urology, aesthetic medicine and cosmetic. To improve and customize its properties and applications, HA can be subjected to chemical modifications: conjugation and crosslinking. The present review gives an overview regarding HA, describing its history, physico-chemical, structural and hydrodynamic properties, and biology -occurrence, biosynthesis (by hyaluronan synthases), degradation (by hyaluronidases and oxidative stress), roles, mechanisms of action and receptors. Furthermore, both conventional and recently emerging methods developed for the industrial production of HA and its chemical derivatization are presented. Finally, the medical, pharmaceutical and cosmetic applications of HA and its derivatives are reviewed, reporting examples of HA-based products which currently are on the market or are undergoing further investigations.

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Section: Ha Degradation In Human Bodymentioning

confidence: 99%

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

Section: Biological Roles Of Ha In Relation To Its Mwmentioning

confidence: 99%

See 3 more Smart Citations

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Fallacara¹,

Baldini²,

Manfredini³

et al. 2018

Preprint

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Hyaluronan‐Based Hydrogels as Modulators of Cellular Behavior

Amorim¹,

Reis²

2022

Multifunctional Hydrogels for Biomedical Applications

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Emerging In Vitro and In Vivo Models: Hope for the Better Understanding of Cancer Progression and Treatment

Yadav,

Mahajan,

Singh

et al. 2024

Advanced Biology

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Various cancer models have been developed to aid the understanding of the underlying mechanisms of tumor development and evaluate the effectiveness of various anticancer drugs in preclinical studies. These models accurately reproduce the critical stages of tumor initiation and development to mimic the tumor microenvironment better. Using these models for target validation, tumor response evaluation, resistance modeling, and toxicity comprehension can significantly enhance the drug development process. Herein, various in vivo or animal models are presented, typically consisting of several mice and in vitro models ranging in complexity from transwell models to spheroids and CRISPR‐Cas9 technologies. While in vitro models have been used for decades and dominate the early stages of drug development, they are still limited primary to simplistic tests based on testing on a single cell type cultivated in Petri dishes. Recent advancements in developing new cancer therapies necessitate the generation of complicated animal models that accurately mimic the tumor's complexity and microenvironment. Mice make effective tumor models as they are affordable, have a short reproductive cycle, exhibit rapid tumor growth, and are simple to manipulate genetically. Human cancer mouse models are crucial to understanding the neoplastic process and basic and clinical research improvements. The following review summarizes different in vitro and in vivo metastasis models, their advantages and disadvantages, and their ability to serve as a model for cancer research.

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Size Matters: Molecular Weight Specificity of Hyaluronan Effects in Cell Biology

Cited by 334 publications

References 93 publications

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Hyaluronan‐Based Hydrogels as Modulators of Cellular Behavior

Emerging In Vitro and In Vivo Models: Hope for the Better Understanding of Cancer Progression and Treatment

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