Danger matrix molecules orchestrate CD14/CD44 signaling in cancer development

Roedig, Heiko; Damiescu, Roxana; Zeng-Brouwers, Jinyang; Kutija, Iva; Trebicka, Jonel; Wygrecka, Małgorzata; Schaefer, Liliana

doi:10.1016/j.semcancer.2019.07.026

Cited by 48 publications

(48 citation statements)

References 282 publications

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“…No doubt interaction with the TLRs for versican, and maybe hyaluronan as well, involves a complex with molecules that have an affinity for the TLRs (113). In addition, it is interesting to compare the consequences of postulated versican-TLR interactions to other proteoglycans that have peptide motifs that bind TLRs, such as biglycan (18,124). Whereas biglycan impacts inflammation by activating TLR4 and inflammasomes through activation of Trif-dependent signaling pathways (4,6,14,19,125), versican appears to mediate TLR2 interaction and activate MyD88-dependent signaling (118,119).…”

Section: Versican: a Component Of The Inflammatory Responsementioning

confidence: 99%

Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation

et al. 2020

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Section: Versican: a Component Of The Inflammatory Responsementioning

confidence: 99%

Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation

et al. 2020

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“…HA is a polysaccharide composed of disaccharide units of d-glucuronic acid, alternating with N-acetyl d-glucosamine (NAG), and it is a component of the ECM and synovial fluids. It is anionic, biodegradable, non-toxic, non-immunogenic, and has been used in targeting CD44, which is highly expressed by a variety of tumors [63]. HA-PEI/PEG NPs have been developed by Ganesh and colleagues to carry siRNAs targeting the protein SSB and PLK1, demonstrating in vivo siRNA activity in xenograft tumor models.…”

Section: Pei-derived Nanosystemsmentioning

confidence: 99%

Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

2020

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RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient’s therapeutic response.

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“…CD44 is dramatically overexpressed on the surface of activated macrophages found at sites of inflammation, as such, it has been widely used as a receptor for targeted drug delivery (81-83). Given the relationship between CS and CD44, CS can be used to modify nanoparticles to enhance the cellular uptake of nanoparticles via CD44-mediated endocytosis (84,85).…”

Section: Cd44mentioning

confidence: 99%

“…Therefore, biglycan core protein plays a pivotal role in the suppression of inflammation and the transition from innate to adaptive immunity (116). Recently, an excellent review reported that biglycan, HA, and versican as the matrix-derived DAMPs regulate TLR-, CD14-, and CD44-signaling cross talk between inflammation and autophagy (85).…”

Section: Biglycanmentioning

confidence: 99%

Regulation of Macrophage and Dendritic Cell Function by Chondroitin Sulfate in Innate to Antigen-Specific Adaptive Immunity

Hatano

Watanabe

2020

Front. Immunol.

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Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a linear acidic polysaccharide comprised of repeating disaccharides, modified with sulfate groups at various positions. Except for hyaluronan (HA), GAGs are covalently bound to core proteins, forming proteoglycans (PGs). With highly negative charges, GAGs interact with a variety of physiologically active molecules, including cytokines, chemokines, and growth factors, and control cell behavior during development and in the progression of diseases, including cancer, infections, and inflammation. Heparan sulfate (HS), another type of GAG, and HA are well reported as regulators for leukocyte migration at sites of inflammation. There have been many reports on the regulation of immune cell function by HS and HA; however, regulation of immune cells by CS has not yet been fully understood. This article focuses on the regulatory function of CS in antigen-presenting cells, including macrophages and dendritic cells, and refers to CSPGs, such as versican and biglycan, and the cell surface proteoglycan, syndecan.

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Danger matrix molecules orchestrate CD14/CD44 signaling in cancer development

Cited by 48 publications

References 282 publications

Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation

Versican—A Critical Extracellular Matrix Regulator of Immunity and Inflammation

Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

Regulation of Macrophage and Dendritic Cell Function by Chondroitin Sulfate in Innate to Antigen-Specific Adaptive Immunity

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