CS Chains Research Articles

Horseradish Peroxidase Immobilized on Multifunctional Hybrid Microspheres for Aflatoxin B1 Removal: Will Enzymatic Reaction be Enhanced by Adsorption?

As the most dangerous carcinogens, efficient and green removal of Aflatoxin B1 (AFB1) is imperative. For the first time, horseradish peroxidase (HRP) was immobilized in/on an alginate/chitosan/montmorillonite (SA/CS/MON) hybrid microsphere and applied for the AFB1 removal. Compared to the enzyme immobilization via encapsulation and adsorption followed by cross-linking, HRP immobilized on the microsphere surface via covalent bonding showed the highest specific activity and AFB1 removal efficiency. The negatively charged MON could not only adsorb abundant AFB1 but also attract more CS chains on the microsphere surface and bring more active sites for enzyme immobilization and cross-linking; thus, the SA/CS/MON microspheres had stronger antiswelling ability and higher AFB1 adsorption capacity and enzyme loading. Although the AFB1 enrichment in the hybrid microsphere did not promote its degradation by enzymatic catalysis, the HRP-loaded hybrid microsphere could be reused and the enzymatic degradation of AFB1 i...

Chondroitin sulfate-D promotes neurite outgrowth by acting as an extracellular ligand for neuronal integrin αVβ3

BackgroundChondroitin sulfate (CS) chains are prominent extra/pericellular matrix components in the central nervous system (CNS) and can exert positive or negative regulatory effects on neurite outgrowth, depending on the CS structure and the amount. Despite the remarkable abilities of highly sulfated forms of CS chains to enhance neurite outgrowth, the neuronal recognition systems for such promotional CS chains, including CS-D polysaccharide, remain to be fully elucidated. MethodsWe explored the molecular basis of the CS-D-mediated neurite extension using primary hippocampal neurons cultured on substrate precoated with CS-D polysaccharides, and evaluated functional involvement of a distinct integrin heterodimer as a novel neuronal CS receptor for CS-D. ResultsWe identified an extracellular matrix receptor, integrin αVβ3, as a functional receptor for CS-D. CS-D, but not CS-C (a precursor form of CS-D) showed significant binding affinity toward recombinant integrin αVβ3 heterodimer and activated intracellular signaling(s) involving focal adhesion kinase (FAK) and Src/Fyn kinase. Functional blockade of the respective players for integrin signaling abrogated the promotional effects of CS-D. We also found the existence of CS-D-induced integrin activation system in neuronal stem/progenitor cell population. ConclusionsThe neuronal cell surface integrin αVβ3 can function as a CS receptor for a highly sulfated CS subtype, CS-D. General significanceOur findings are the first to demonstrate that CS-dependent neurite outgrowth promotion is exerted via direct activation of specific integrin heterodimers on neuronal cell surfaces, providing new insights into understanding the CS-sensing machineries that regulate CNS development and regeneration.

Chitosan Nanocapsules for pH‐Triggered Dual Release Based on Corrosion Inhibitors as Model Study

AbstractChitosan (CS) is known for its uniqueness in terms of containing reactive functional groups, i.e., amino and hydroxyl groups, along the chain which offer the noncovalent bonds and chemical modifications. At pH 3 in emulsion system, the CS chains are under charge‐charge repulsive force, leading the polysaccharide chains to align as the hollow nanospheres and at that time, the crosslink leads to the nanocapsules. The CS nanocapsules allow the model cargos, i.e., corrosion inhibitors, entrapment not only via the noncovalent bond based on the weak interaction in the core for 2‐mercaptobenzothiazole (MBT) cargo but also via the chemical bonds based on the amino group remaining on CS structure to result in either amide or Schiff base linkage in case of 3‐nitrosalicylic acid (3NiSA) cargo. The release studies indicate that CS nanocapsules can release two cargoes upon pH change due to the acidic/basic‐triggered cleavage of bonds between cargoes and nanocapsules. Once corrosion occurs, resulting in variation of the local pH value, the CS nanocapsules release MBT in fast and 3NiSA in a slow, sustained manner. The efficiency of the approach is demonstrated using the nanocapsules for hindering the corrosion of copper as measured by electrochemical quartz crystal microbalance.

Synthesis of chitosan/poly (ethylene glycol)-modified magnetic nanoparticles for antibiotic delivery and their enhanced anti-biofilm activity in the presence of magnetic field

Biocompatible Fe3O4/chitosan (CS)/poly (ethylene glycol) (PEG)/gentamicin (Gent) magnetic nanoparticles, namely Fe3O4@PEG-Gent NPs, have been successfully developed for antibiotic delivery. In which, PEG dicarboxylic acid was used to modify Fe3O4 NPs for good dispersity as well as offer sufficient carboxyl groups as binding sites. And then the free Gent was facilely loaded onto Fe3O4 NPs so as to achieve powerful antibacterial activity via electrostatic interactions. Under acidic condition, the CS and PEG of Fe3O4@PEG-Gent were protonated to introduce the positive charge to NPs surface, thus facilitating the contact with negatively charged bacterial cell membrane. What is more, the stretches of CS chains triggered by acidic pH may prevent the antimicrobial efficiency of Gent from weakening. Compared with the free antibiotic, these nanocomposites presented better antimicrobial efficacy against gram-positive bacteria S. aureus under acidic condition. Intriguingly, the confocal laser scanning macroscopy imaging suggested that the anti-biofilm efficacy of nanocomposites was significantly enhanced in the presence of an external magnetic field. Due to the superparamagnetic performance of Fe3O4 NPs, these nanocomposites were allowed deeper penetration into a mature biofilm of S. aureus by magnetic field, leading to an effective Gent delivery for eradication of biofilm. The ingenious fabrication of the antibiotic delivery system not only efficiently improved the effectiveness and bioavailability of Gent at acidic media, but also provided an innovative platform to treat bacterial biofilms-associated infection by applying extra environmental factors such as magnetic field.

Surface-modified PLGA nanoparticles with chitosan for oral delivery of tolbutamide

The main purpose of present study was to develop novel chitosan-modified polylactic-co-glycolicacid nanoparticles (CS@PLGA NPs) for improving the bio-availability of tolbutamide (TOL). The TOL-loaded CS@PLGA NPs (TOL-CS@PLGA NPs) were fabricated with the solvent evaporation method. The cargo-free CS@PLGA NPs showed a diameter of 228.3±2.5nm monitored with a laser light particlesizer, and the transmission electron microscope (TEM) photographs revealed their “core-shell” structures. The Zeta potential of the original PLGA NPs and the cargo-free CS@PLGA NPs was measured to be −20.2±3.21mV and 24.2±1.1mV, respectively. The changes in Zeta potential indicated the CS chains were coated on the surfaces of the original PLGA NPs. The thermal gravity analysis (TGA) curves suggested that the CS chains improved the thermostability of the original PLGA NPs. The results of cells viability indicated the cargo-free CS@PLGA NPs were nontoxicity. The in vitro release profiles suggested that TOL-CS@PLGA NPs could release TOL in pH 7.4 phosphate buffer solution (PBS) at a sustained manner. Streptozotocin (STZ) was employed to build the diabetic rat models. The physiological changes in the islet β cells confirmed the obtaining of diabetic rats. After treatment by gavage, the TOL-CS@PLGA NPs showed an excellent hypoglycemic effect. Therefore, the TOL-CS@PLGA NPs had a potential application in oral delivery of TOL.

Incorporation of lysozyme-rectorite composites into chitosan films for antibacterial properties enhancement

The demand for designing antibacterial materials was quite substantial in packing and biomedical materials fields. Chitosan had a wide utilization to satisfy this demand. In this study, by incorporating lysozyme (LY) – rectorite (REC) into chitosan films, the ultimately obtained hybrid films can own the enhanced antibacterial properties and still remains good mechanical properties. Scanning electron microscopy (SEM) images revealed that LY and REC could be homogeneously distributed in the CS films. X-ray photoelectron spectroscopy (XPS) and Energy-dispersive X-ray analysis (EDX) results verified that the LY-REC incorporation process was successful. Small angle X-ray diffraction (SAXRD) and Fourier transform infrared (FT-IR) spectra revealed that some intercalation reactions occurred between CS chains and REC. The hydrophobic properties of the CS films were increased by the addition of LY and REC, determined by water contact angle measurement. In comparison with CS films, the mechanical properties of the composite films after adding LY-REC were reduced by 27.58%, but still maintained high tensile strength. Besides, the antibacterial properties of the films could be enhanced by introducing LY-REC. This method exhibited great application value in the food packaging fields.

HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix.

Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries.

Proton conductivity and relaxation properties of chitosan-acetate films

The effect of aqueous acetic acid solution concentration during the preparation of chitosan-acetate (CS-acetate) films on the conductivity and relaxation properties were studied by dielectric and FTIR spectroscopies, TGA measurements and X-Ray diffraction. Analyses of the experimental results on the degree of deacetylation, water absorption, conductivity, Vogel temperature and activation energy demonstrate a strong dependence of these parameters on the concentration of the acid acetic solutions from which the films have been obtained. The proton conductivity and relaxation properties of CS-acetate films have been interpreted using two Grotthuss “structural diffusion” and “pack-acid” mechanisms. The transformation between these two mechanisms observed at temperature higher than CS-acetate glass transition temperature is due to an increase in the thermal motion of CS chains, water evaporation, hydrogen bond between water molecules and side groups of CS breaking and formation of new bonds between NH3+ and acetate ions. Additionally, application of the Rice and Roth model allowed estimating the temperature dependence of proton number and their mobility in CS-acetate films. A systematic interpretation on the appropriate conductivity mechanism will help trigger the design of smart materials used in flexible electronic, solid polymer electrolytes for fuel cells and solid polymer batteries based on CS-acetate films.

Role of Chondroitin Sulfate (CS) Modification in the Regulation of Protein-tyrosine Phosphatase Receptor Type Z (PTPRZ) Activity: PLEIOTROPHIN-PTPRZ-A SIGNALING IS INVOLVED IN OLIGODENDROCYTE DIFFERENTIATION

Protein-tyrosine phosphatase receptor type Z (PTPRZ) is predominantly expressed in the developing brain as a CS proteoglycan. PTPRZ has long (PTPRZ-A) and short type (PTPRZ-B) receptor forms by alternative splicing. The extracellular CS moiety of PTPRZ is required for high-affinity binding to inhibitory ligands, such as pleiotrophin (PTN), midkine, and interleukin-34; however, its functional significance in regulating PTPRZ activity remains obscure. We herein found that protein expression of CS-modified PTPRZ-A began earlier, peaking at approximately postnatal days 5-10 (P5-P10), and then that of PTN peaked at P10 at the developmental stage corresponding to myelination onset in the mouse brain. Ptn-deficient mice consistently showed a later onset of the expression of myelin basic protein, a major component of the myelin sheath, than wild-type mice. Upon ligand application, PTPRZ-A/B in cultured oligodendrocyte precursor cells exhibited punctate localization on the cell surface instead of diffuse distribution, causing the inactivation of PTPRZ and oligodendrocyte differentiation. The same effect was observed with the removal of CS chains with chondroitinase ABC but not polyclonal antibodies against the extracellular domain of PTPRZ. These results indicate that the negatively charged CS moiety prevents PTPRZ from spontaneously clustering and that the positively charged ligand PTN induces PTPRZ clustering, potentially by neutralizing electrostatic repulsion between CS chains. Taken altogether, these data indicate that PTN-PTPRZ-A signaling controls the timing of oligodendrocyte precursor cell differentiation in vivo, in which the CS moiety of PTPRZ receptors maintains them in a monomeric active state until its ligand binding.

Facile preparation of biphasic-induced magnetic icariin-loaded composite microcapsules by automated in situ click technology

This research aims to prepare the biphasic-induced magnetic composite microcapsules (BIMCM) as a promising environmental stimuli-responsive delivery vehicle to dispose the problem of drug burst effect. The paper presented a novel automated in situ click technology of magnetic chitosan/nano hydroxyapatite (CS/nHA) microcapsules. Fe3O4 magnetic nanoparticles (MNP) and nHA were simultaneously in situ crystallized by one-step process. Icariin (ICA), a plant-derived flavonol glycoside, was combined to study drug release properties of BIMCM. BIMCM were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and Thermal gravimetric analysis/Differential Scanning Calorimetry(TGA/DSC) in order to reveal their component and surface morphology as well as the role of the in situ generated Fe3O4 MNP and nHA. The magnetic test showed the BIMCM were super-paramagnetic. Both in situ generated Fe3O4 MNP and nHA serve as stable inorganic crosslinkers in BIMCM to form many intermolecular crosslinkages for the movability of the CS chains. This makes ICA loaded microcapsules take on a sustained release behavior and results in the self-adjusting of surface morphology, decreasing of swelling and degradation rates. In addition, in vitro tests were systematically carried out to examine the biocompatibility of the microcapsules by MTT test, Wright-Giemsa dying assay and AO/EB fluorescent staining method. These results demonstrated that successful introduction of the in situ click Fe3O4 MNP provided an alternative strategy because of magnetic sensitivity and sustained release. As such, the novel ICA loaded biphasic-induced magnetic CS/nHA/MNP microcapsules are expected to find potential applications in drug delivery system for bone repair.

Catabolism of chondroitin sulfate.

Chondroitin sulfate (CS) is a ubiquitous component of the cell surface and extracellular matrix of animal tissues. CS chains are covalently bound to a core protein to form a proteoglycan, which is involved in various biological events including cell proliferation, migration, and invasion. Their functions are executed by regulating the activity of bioactive proteins, such as growth factors, morphogens, and cytokines. This review article focuses on the catabolism of CS. This catabolism predominantly occurs in lysosomes to control the activity of CS-proteoglycans. CS chains are fragmented by endo-type glycosidase(s), and the resulting oligosaccharides are then cleaved into monosaccharide moieties from the nonreducing end by exoglycosidases and sulfatases. However, the endo-type glycosidase responsible for the systemic catabolism of CS has not yet been identified. Based on recent advances in studies on hyaluronidases, which were previously considered to be hyaluronan-degrading enzymes, it appears that they recognize CS as their original substrate rather than hyaluronan and acquired hyaluronan-hydrolyzing activity at a relatively late stage of evolution.

Identification of Chondroitin Sulfate Linkage Region Glycopeptides Reveals Prohormones as a Novel Class of Proteoglycans

Vertebrates produce various chondroitin sulfate proteoglycans (CSPGs) that are important structural components of cartilage and other connective tissues. CSPGs also contribute to the regulation of more specialized processes such as neurogenesis and angiogenesis. Although many aspects of CSPGs have been studied extensively, little is known of where the CS chains are attached on the core proteins and so far, only a limited number of CSPGs have been identified. Obtaining global information on glycan structures and attachment sites would contribute to our understanding of the complex proteoglycan structures and may also assist in assigning CSPG specific functions. In the present work, we have developed a glycoproteomics approach that characterizes CS linkage regions, attachment sites, and identities of core proteins. CSPGs were enriched from human urine and cerebrospinal fluid samples by strong-anion-exchange chromatography, digested with chondroitinase ABC, a specific CS-lyase used to reduce the CS chain lengths and subsequently analyzed by nLC-MS/MS with a novel glycopeptide search algorithm. The protocol enabled the identification of 13 novel CSPGs, in addition to 13 previously established CSPGs, demonstrating that this approach can be routinely used to characterize CSPGs in complex human samples. Surprisingly, five of the identified CSPGs are traditionally defined as prohormones (cholecystokinin, chromogranin A, neuropeptide W, secretogranin-1, and secretogranin-3), typically stored and secreted from granules of endocrine cells. We hypothesized that the CS side chain may influence the assembly and structural organization of secretory granules and applied surface plasmon resonance spectroscopy to show that CS actually promotes the assembly of chromogranin A core proteins in vitro. This activity required mild acidic pH and suggests that the CS-side chains may also influence the self-assembly of chromogranin A in vivo giving a possible explanation to previous observations that chromogranin A has an inherent property to assemble in the acidic milieu of secretory granules.

Mechanically reinforced chitosan/cellulose nanocrystals composites with good transparency and biocompatibility

Chitosan/cellulose nanocrystals (CS/CNCs) composites were prepared with different contents of CNCs. Due to the homogeneous dispersion of CNCs and the strong interfacial interactions resulting from hydrogen bonding between CS chains and CNCs, the transparency of CS is well retained and the overall mechanical properties of CS are significantly improved. Furthermore, because both CS and CNCs are biocompatible materials, cell proliferation test shows that the obtained composites are noncytotoxic and can potentially meet safety requirements of biomedical applications. These advantages pave the way of potential applications of CS in the field of commercial plastics and encourage the use of CS as environment-friendly material and biomedical material.

Biocompatible core–shell electrospun nanofibers as potential application for chemotherapy against ovary cancer

Polyvinyl alcohol/chitosan (PVA/CS) core–shell nanofibers are successfully fabricated by a simple coaxial electrospinning method, in which PVA forms the core layer and CS forms the shell layer. With the change of the feed ratio between PVA and CS, the surface morphology and the microstructures of the nanofibers are largely changed. The as-prepared core–shell fibers can be used as a carrier for doxorubicin (DOX) delivery. FT-IR analysis demonstrates that hydrogen bond between CS and PVA chains forms. The results of in vitro cytotoxicity test indicate that the core–shell fibers are completely biocompatible and the free DOX shows higher cytotoxicity than the DOX loaded nanofibers. The standing PVA/CS core–shell fibers remarkably promote the attachment, proliferation and spreading of human ovary cancer cells (SKOV3). Via observing by confocal laser scanning microscopy (CLSM), the DOX released from the fibers can be delivered into SKOV3 cell nucleus, which is significant for the future tumor therapy. And, the as-prepared fibers exhibit controlled release for loaded DOX via adjusting the feed ratio between PVA and CS, and the DOX loaded nanofibers are quite effective in prohibiting the SKOV3 ovary cells attachment and proliferation, which are potential for chemotherapy of ovary cancer.

Synthesis, characterization and antimicrobial activity of biodegradable conducting polypyrrole-graft-chitosan copolymer

In this study, polypyrrole-graft-chitosan (PPy-g-CS) copolymer was chemically synthesized and its structural and morphological properties characterized by FTIR, UV–vis, SEM, XRD, TGA and zeta-potential techniques. The results revealed that there were strong interactions between PPy and CS chains. The electrical conductivity of CS increased to semiconducting range by grafting. The crystallinity and thermal stability of PPy-g-CS copolymer improved when compared to CS. The copolymer was tested against various bacterial and fungal strains at various concentrations and results obtained were compared with the reference antibiotics. The results indicated that the antibacterial activity of PPy-g-CS copolymer was stronger than CS and PPy alone. The antibacterial activity of the PPy-g-CS copolymer observed to increase with rising concentration, and showed stronger activity against bacteria than Penicillin (10mg), Rifampicin (5mg) and Trimethoprim (25mg), whereas showed equipotent activity with Amikacin (30mg) and Erythromycin (15mg) antibiotics.

Enhanced proton conduction of chitosan membrane enabled by halloysite nanotubes bearing sulfonate polyelectrolyte brushes

Currently, enhancing the proton conductivity is one challenge for chitosan (CS, an industrial waste around the world) membrane to work as proton exchange membrane for direct methanol fuel cell. In this study, halloysite nanotubes bearing sulfonate polyelectrolyte brushes (SHNTs) are synthesized via distillation–precipitation polymerization and then incorporated into CS matrix to fabricate nanohybrid membranes. The membranes are characterized using field emission scanning electron microscope, fourier transform infrared, thermogravimetric analysis, differential scanning calorimetry, and mechanical tester. It is found that SHNTs generate strong electrostatic attractions to CS chains, which inhibit the chain mobility and thus enhance the thermal and mechanical stabilities of nanohybrid membranes. The results of water uptake, area swelling, proton conductivity, and activation energy reveal that the high aspect nanotube and long polyelectrolyte brush allow SHNTs to construct continuous and wide pathways, along which sulfonic acid–amide acid–base pairs are formed and work as low-barrier proton-hoping sites, imparting an enhanced proton transfer via Grotthuss mechanism. In such a way, the proton conductivity of CS membrane is obviously enhanced, and 15% SHNTs can afford a 60% enhancement in conductivity to the nanohybrid membrane, particularly. Moreover, the methanol permeability and selectivity of the as-prepared membranes are investigated in detail.

Graphene oxide–chitosan composite hydrogels as broad-spectrum adsorbents for water purification

Water pollution is one of the most pervasive problems afflicting people throughout the world, while adsorption is the most widely used method to remove the contaminants from water. Here, in this paper, we report an eco-friendly graphene oxide–chitosan (GO–CS) hydrogel as a new type of adsorbent for water purification. The GO–CS hydrogels were prepared via self-assembly of GO sheets and CS chains. A three-dimensional network composed of GO sheets crosslinked by CS was found in GO–CS hydrogels. The GO–CS composite hydrogels showed high adsorption capacity towards different contaminants, including cationic and anionic dyes, as well as heavy metal ions. The mechanism of the dye adsorption was investigated with a spectral method, and an electrostatic interaction was found to be the major interaction between ionic dyes and the hydrogel. The influence of the hydrogel composition on the adsorption capacity towards different adsorbates was also studied. Finally, it was demonstrated that the GO–CS hydrogel can be used as column packing, to fabricate a column for water purification by filtration.

Preparation and characterization of UV-sensitive chitosan for UV-cure with poly(ethylene glycol) dimethacrylate

In this study, gel membranes of chitosan-g-poly(ethylene glycol) dimethacrylate (CS-g-PEGDMA) with pH sensitive properties were synthesized without employing any photo-initiator and crosslinker. First, CS was endowed with UV-sensitive property by reaction with cinnamoyl chloride in methanesulfonic acid. The reaction mainly occurred on the hydroxyl groups of the pyranose unit, while most C-2 amino groups were protected. The substitution degree of cinnamoyl group was 0.98, while the protection efficiency of –NH2 was about 80 %. Upon UV-irradiation, initial free radicals were produced only along the cinnamoyl-modified CS chains, which induced the grafting of PEGDMA from the chitosan chains and eventually the crosslinking. Increasing the feeding amount of PEGDMA increased the grafting ratio as well as the crosslinking density. The Tg value decreased from 161 °C for the pure chitosan to about 90 °C for the CS-g-PEGDMA with a grafting ratio of 1.29. Two stages of degradation correspondent to the individual degradation of CS chains and the PEGDMA chains were observed for all CS-g-PEGDMA copolymers, demonstrating their nature of graft copolymers. The tensile mechanical properties of the CS-g-PEGDMA membranes were affected by the two opposing factors: inter-connected soft PEGDMA chains and crosslinking density; and the optimum properties were achieved when the grafting ratio was increased to about 0.80. By combining CS and PEGDMA components, these copolymer membranes thus have the potential to be used as biomedical membranes.

Receptor for Advanced Glycation End Products Functions as a Receptor for Glycosaminoglycans in Lung Metastasis

Glycosaminoglycans (GAGs) at cell surfaces of cancer cells play roles in malignant transformation and metastasis. Highly metastatic Lewis lung carcinoma cells showed a strong expression of the chondroitin sulfate E (CS‐E) epitope consisting of the E‐disaccharide unit GlcUA‐GalNAc(4, 6‐O‐disulfate). The metastasis was efficiently inhibited in a mouse system by enzymatic removal of CS from the tumor cell surface or by pre‐injection of CS‐E in a dose‐dependent manner (Li et al., J. Biol. Chem. 2008). These findings prompted us to investigate the roleof the CS and/or GAG structure of the tumor cells in the experimental lung metastasis.In this study to characterize CS‐E‐binding proteins in a mouse lung, an extract of a mouse lung homogenate was analyzed by affinity chromatography using a CS‐E‐immobilized column. A CS‐E‐binding putative receptor was identified as Receptor for Advanced Glycation End products (RAGE) by SDS‐PAGE followed by MALDI‐TOF‐MS of the trypsin digest of a protein band, suggesting that the E‐unit‐containing epitopes of CS chains as well as heparan sulfate chains at the tumor cell surfaces are recognized by RAGE in the lung, and are promising targets for diagnosis and therapy of malignant tumors (S. Mizumoto, J. Takahashi, and K. Sugahara, submitted).This work was supported by a Grant‐in‐aid for Scientific Research (B) and Future Drug Discovery and Medical Care Innovation Program from MEXT (to KS).

A Structural Analysis of Glycosaminoglycans from Lethal and Nonlethal Breast Cancer Tissues: Toward a Novel Class of Theragnostics for Personalized Medicine in Oncology?

Cancer is one of the leading noncommunicable diseases that vastly impacts both developed and developing countries. Truly innovative diagnostics that inform disease susceptibility, prognosis, and/or response to treatment (theragnostics) are seriously needed for global public health and personalized medicine for patients with cancer. This study examined the structure and content of glycosaminoglycans (GAGs) in lethal and nonlethal breast cancer tissues from six patients. The glycosaminoglycan content isolated from tissue containing lethal cancer tumors was approximately twice that of other tissues. Molecular weight analysis showed that glycosaminoglycans from cancerous tissue had a longer weight average chain length by an average of five disaccharide units, an increase of approximately 15%. Dissacharide analysis found differences in sulfation patterns between cancerous and normal tissues, as well as sulfation differences in GAG chains isolated from patients with lethal and nonlethal cancer. Specifically, cancerous tissue showed an increase in sulfation at the "6S" position of CS chains and an increase in the levels of the HS disaccharide NSCS. Patients with lethal cancer showed a decrease in HS sulfation, with lower levels of "6S" and higher levels of the unsulfated "0S" disaccharide. Although these findings come from a limited sample size, they indicate that structural changes in GAGs exist between cancerous and noncancerous tissues and between tissues from patients with highly metastatic cancer and cancer that was successfully treated by chemotherapy. Based on these findings, we hypothesize that (1) there are putative changes in the body's construction of GAGs as tissue becomes cancerous; (2) there may be innate structural person-to-person variations in GAG composition that facilitate the metastasis of tumors in some patients when they develop cancer.