Utilization of Glycosaminoglycans/Proteoglycans as Carriers for Targeted Therapy Delivery

Misra, Suniti; Hascall, Vincent C.; Atanelishvili, Ilia; Rodríguez, Ricardo Moreno; Markwald, Roger R.; Ghatak, Shibnath

doi:10.1155/2015/537560

Cited by 26 publications

(13 citation statements)

References 256 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therapies that target the ECM provide a promising approach to overcome chemoresistance either by preventing ECM-conferred chemoresistance or by altering the ECM such that current therapies can overcome physical treatment limits [ 200 , 201 , 202 , 203 , 204 ]. It has been shown that the dense ECM can inhibit therapeutic drug penetration, diffusion and transport, thus the ECM acts as a barrier to drug delivery [ 205 , 206 , 207 , 208 , 209 , 210 , 211 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

Senthebane

Jonker

Rowe

et al. 2018

IJMS

113

176

View full text Add to dashboard Cite

Background: The functional interplay between tumor cells and their adjacent stroma has been suggested to play crucial roles in the initiation and progression of tumors and the effectiveness of chemotherapy. The extracellular matrix (ECM), a complex network of extracellular proteins, provides both physical and chemicals cues necessary for cell proliferation, survival, and migration. Understanding how ECM composition and biomechanical properties affect cancer progression and response to chemotherapeutic drugs is vital to the development of targeted treatments. Methods: 3D cell-derived-ECMs and esophageal cancer cell lines were used as a model to investigate the effect of ECM proteins on esophageal cancer cell lines response to chemotherapeutics. Immunohistochemical and qRT-PCR evaluation of ECM proteins and integrin gene expression was done on clinical esophageal squamous cell carcinoma biopsies. Esophageal cancer cell lines (WHCO1, WHCO5, WHCO6, KYSE180, KYSE 450 and KYSE 520) were cultured on decellularised ECMs (fibroblasts-derived ECM; cancer cell-derived ECM; combinatorial-ECM) and treated with 0.1% Dimethyl sulfoxide (DMSO), 4.2 µM cisplatin, 3.5 µM 5-fluorouracil and 2.5 µM epirubicin for 24 h. Cell proliferation, cell cycle progression, colony formation, apoptosis, migration and activation of signaling pathways were used as our study endpoints. Results: The expression of collagens, fibronectin and laminins was significantly increased in esophageal squamous cell carcinomas (ESCC) tumor samples compared to the corresponding normal tissue. Decellularised ECMs abrogated the effect of drugs on cancer cell cycling, proliferation and reduced drug induced apoptosis by 20–60% that of those plated on plastic. The mitogen-activated protein kinase-extracellular signal-regulated kinase (MEK-ERK) and phosphoinositide 3-kinase-protein kinase B (PI3K/Akt) signaling pathways were upregulated in the presence of the ECMs. Furthermore, our data show that concomitant addition of chemotherapeutic drugs and the use of collagen- and fibronectin-deficient ECMs through siRNA inhibition synergistically increased cancer cell sensitivity to drugs by 30–50%, and reduced colony formation and cancer cell migration. Conclusion: Our study shows that ECM proteins play a key role in the response of cancer cells to chemotherapy and suggest that targeting ECM proteins can be an effective therapeutic strategy against chemoresistant tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

Senthebane

Jonker

Rowe

et al. 2018

IJMS

113

176

View full text Add to dashboard Cite

show abstract

“…The majority of PGs contain both O ‐ and N ‐type of glycans; however, as the O ‐glycan chain(s), called GAGs are much larger, representing more than a half of the PG MW, the properties and the biological activities of PGs are basically given by GAGs. Due to these carbohydrate chains, often hybrid, PGs are involved in various cellular signaling processes , and interact with many protein enzymes and growth factors (GFs). Minor changes into the fine structure of GAGs, which occur during the physiological process of maturation and aging, may trigger a series of biological events among which also the occurrence of cancer .…”

Section: General Considerations On the Structure And Functions Of Gagsmentioning

confidence: 99%

Applications of capillary electrophoresis electrospray ionization mass spectrometry in glycosaminoglycan analysis

Zamfir

2016

ELECTROPHORESIS

View full text Add to dashboard Cite

Proteoglycans (PGs) represent a class of heavily glycosylated proteins distributed in the extracellular matrix, connective tissues, and on the surface of many cell types where, as functional molecules, regulate important biological processes. Structurally, PGs consist of a core protein linked to glycosaminoglycan (GAG) chains, which basically determine the properties and activities of PGs. In view of the structural complexity of GAGs and the existing correlation between this structure and PG functions, systematic efforts are invested into development of analytical methods for GAG characterization. Although less popular and of higher technical difficulty than liquid-based chromatographic methods, CE coupled with ESI MS contributed lately an important progress to glycosaminoglycomics field. In this review article, the most significant CE ESI MS and MS/MS applications in GAG research are highlighted and critically assessed. The advantages and the limitations of each concept as well as the possible further methodological refinements are also concisely discussed. Finally, the review presents the perspectives of CE ESI MS in GAG analysis along with the objectives, which still need to be reached in the near future.

show abstract

“…GAGs interact electrostatically with different compounds or biologics used for therapeutic purposes thanks to their strong negative charge. The drugs are delivered systemically or locally to treat a variety of pathological conditions, including cancer, glaucoma, wounds, and burns ( Misra et al, 2015 ).…”

Section: Glycosaminoglycans As Therapeutic Targetsmentioning

confidence: 99%

Surface Proteoglycans as Mediators in Bacterial Pathogens Infections

et al. 2016

View full text Add to dashboard Cite

Infectious diseases remain an important global health problem. The interaction of a wide range of pathogen bacteria with host cells from many different tissues is frequently mediated by proteoglycans. These compounds are ubiquitous complex molecules which are not only involved in adherence and colonization, but can also participate in other steps of pathogenesis. To overcome the problem of microbial resistance to antibiotics new therapeutic agents could be developed based on the characteristics of the interaction of pathogens with proteoglycans.

show abstract

Utilization of Glycosaminoglycans/Proteoglycans as Carriers for Targeted Therapy Delivery

Cited by 26 publications

References 256 publications

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

Applications of capillary electrophoresis electrospray ionization mass spectrometry in glycosaminoglycan analysis

Surface Proteoglycans as Mediators in Bacterial Pathogens Infections

Contact Info

Product

Resources

About