Mucins as anti-cancer targets: perspectives of the glycobiologist

Brockhausen, Inka; Melamed, Jacob

doi:10.1007/s10719-021-09986-8

Cited by 27 publications

(26 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, as AMPs bind with bacterial membranes, ACPs can bind directly with the cancer cell walls due to their cationic and amphipathic nature ( Ma et al, 2019 ). It has been established that different from normal eukaryotic cell membranes which are made of uncharged neutral phospholipids, sphingomyelins, and cholesterol and are neutral in charge ( Zachowski, 1993 ; Doktorova et al, 2020 ), the surface of the cancer cells is net negatively charged because of increased proportions of anionic phosphatidylserine, heparan, and chondroitin sulfate proteoglycans, O-glycosylated mucins, and sialylated glycoproteins ( Warren, 1974 ; Warren et al, 1979 ; Utsugi et al, 1991 ; Zwaal et al, 2005 ; Calianese and Birge, 2020 ; Brockhausen and Melamed, 2021 ; Hassan et al, 2021 ; Hugonnet et al, 2021 ). ACPs can selectively recognize cancer cells by electrostatic interactions with the negatively charged phospholipids on the surface.…”

Section: How Ll-37 Can Eradicate/affect Cancer?mentioning

confidence: 99%

Renovation as innovation: Repurposing human antibacterial peptide LL-37 for cancer therapy

Zhu

Zhang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

In many organisms, antimicrobial peptides (AMPs) display wide activities in innate host defense against microbial pathogens. Mammalian AMPs include the cathelicidin and defensin families. LL37 is the only one member of the cathelicidin family of host defense peptides expressed in humans. Since its discovery, it has become clear that they have pleiotropic effects. In addition to its antibacterial properties, many studies have shown that LL37 is also involved in a wide variety of biological activities, including tissue repair, inflammatory responses, hemotaxis, and chemokine induction. Moreover, recent studies suggest that LL37 exhibits the intricate and contradictory effects in promoting or inhibiting tumor growth. Indeed, an increasing amount of evidence suggests that human LL37 including its fragments and analogs shows anticancer effects on many kinds of cancer cell lines, although LL37 is also involved in cancer progression. Focusing on recent information, in this review, we explore and summarize how LL37 contributes to anticancer effect as well as discuss the strategies to enhance delivery of this peptide and selectivity for cancer cells.

show abstract

Section: How Ll-37 Can Eradicate/affect Cancer?mentioning

confidence: 99%

Renovation as innovation: Repurposing human antibacterial peptide LL-37 for cancer therapy

Zhu

Zhang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Therefore, and not surprisingly, the field of glycodendrimers, with their intrinsic multivalency and high affinity (avidity), has been exploited in the creation of powerful tools to provide therapeutic applications against cancer [44] that also include theranostics [45]. Several strategies can be applied to address this issue, amongst which, immune cell targeting through their well-studied mannoside receptors such as DC-SIGN [10], anti-carbohydrate antibodies and vaccines [40][41][42][43][44], screening microarrays using dendrimer's increased sensitivity [46,47], and notably anti-cancer vaccines. Interestingly, to this arsenal of glycodendrimers of therapeutic values against cancer, there is an additional avenue that was recently investigated.…”

Section: Heterofunctional Glycodendrimers As Clearing Agents Following Radioimmunotherapymentioning

confidence: 99%

“…Tumor-associated carbohydrate antigens (TACAs), originating from either glycolipids (gangliosides) [ 40 ] or O -linked mucin glycoproteins (MUCs) [ 41 , 42 , 43 , 44 ], have been extensively used as targeting agents for cancer immunotherapy. Therefore, and not surprisingly, the field of glycodendrimers, with their intrinsic multivalency and high affinity (avidity), has been exploited in the creation of powerful tools to provide therapeutic applications against cancer [ 44 ] that also include theranostics [ 45 ].…”

Section: Immune Cell Targeting Immunodiagnostics and Vaccinesmentioning

confidence: 99%

“…As stated above, owing to their over expression in a number of cancer cells, TACAs from the group of O -linked mucins have been the subject of intense activity to generate anti-carbohydrate cancer vaccines [ 41 , 42 , 43 , 44 ]. The group of Bay et al reported a fully synthetic anti-cancer vaccine for human use [ 50 , 51 ].…”

Section: Immune Cell Targeting Immunodiagnostics and Vaccinesmentioning

confidence: 99%

See 1 more Smart Citation

Design, Synthetic Strategies, and Therapeutic Applications of Heterofunctional Glycodendrimers

Mousavifar

Roy

2021

Molecules

View full text Add to dashboard Cite

Glycodendrimers have attracted considerable interest in the field of dendrimer sciences owing to their plethora of implications in biomedical applications. This is primarily due to the fact that cell surfaces expose a wide range of highly diversified glycan architectures varying by the nature of the sugars, their number, and their natural multiantennary structures. This particular situation has led to cancer cell metastasis, pathogen recognition and adhesion, and immune cell communications that are implicated in vaccine development. The diverse nature and complexity of multivalent carbohydrate–protein interactions have been the impetus toward the syntheses of glycodendrimers. Since their inception in 1993, chemical strategies toward glycodendrimers have constantly evolved into highly sophisticated methodologies. This review constitutes the first part of a series of papers dedicated to the design, synthesis, and biological applications of heterofunctional glycodendrimers. Herein, we highlight the most common synthetic approaches toward these complex molecular architectures and present modern applications in nanomolecular therapeutics and synthetic vaccines.

show abstract

“…MUC1 glycoprotein contains a variable number of tandem repeats (VNTRs) region (HGVTSAPDTRPAPGSTAPPA) in its extracellular domain (Gaidzik et al, 2013;Pillai et al, 2015;Li and Li, 2020). With its unique biological features, tumor-associated antigen MUC1 glycoprotein has been considered as one of the favorable targets for the development of cancer immunotherapy (Barratt-Boyes, 1996;Singh and Bandyopadhyay, 2007;Pillai et al, 2015;Dhanisha et al, 2018;Brockhausen and Melamed, 2021). However, the weak immunogenicity of MUC1 limits its development and clinical application (Tang et al, 2008;Tang et al, 2018;Chen et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

MUC1 Specific Immune Responses Enhanced by Coadministration of Liposomal DDA/MPLA and Lipoglycopeptide

Zhou

Cheng

et al. 2022

Front. Chem.

View full text Add to dashboard Cite

Mucin 1 (MUC1), a well-known tumor-associated antigen and attractive target for tumor immunotherapy, is overexpressed in most human epithelial adenomas with aberrant glycosylation. However, its low immunogenicity impedes the development of MUC1-targeted antitumor vaccines. In this study, we investigated three liposomal adjuvant systems containing toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) and auxiliary lipids of different charges: cationic lipid dimethyldioctadecylammonium (DDA), neutral lipid distearoylglycerophosphocholine (DSPC) or anionic lipid dioleoylphosphatidylglycerol (DOPG), respectively. ELISA assay evidenced that the positively charged DDA/MPLA liposomes are potent immune activators, which induced remarkable levels of anti-MUC1 antibodies and exhibited robust Th1-biased immune responses. Importantly, the antibodies induced by DDA/MPLA liposomes efficiently recognized and killed MUC1-positive tumor cells through complement-mediated cytotoxicity. In addition, antibody titers in mice immunized with P2-MUC1 vaccine were significantly higher than those from mice immunized with P1-MUC1 or MUC1 vaccine, which indicated that the lipid conjugated on MUC1 antigen also played important role for immunomodulation. This study suggested that the liposomal DDA/MPLA with lipid-MUC1 is a promising antitumor vaccine, which can be used for the immunotherapy of various epithelial carcinomas represented by breast cancer.

show abstract

Mucins as anti-cancer targets: perspectives of the glycobiologist

Cited by 27 publications

References 126 publications

Renovation as innovation: Repurposing human antibacterial peptide LL-37 for cancer therapy

Renovation as innovation: Repurposing human antibacterial peptide LL-37 for cancer therapy

Design, Synthetic Strategies, and Therapeutic Applications of Heterofunctional Glycodendrimers

MUC1 Specific Immune Responses Enhanced by Coadministration of Liposomal DDA/MPLA and Lipoglycopeptide

Contact Info

Product

Resources

About