Structure and function of glycosphingolipids on small extracellular vesicles

He, Xin; Guan, Feng; Lei, Lei

doi:10.1007/s10719-022-10052-0

Cited by 13 publications

(11 citation statements)

References 89 publications

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“…These results point to other relevant biological locations where gangliosides may serve as Siglec ligands, such as on EVs and viruses. Gangliosides are found ubiquitously across all cell types and tissues and contribute to the composition of EVs 67 . Siglec-1 23 and -7 26 , 50 have both been shown to engage EVs in a manner that is predicted to be through glycolipids.…”

Section: Discussionmentioning

confidence: 99%

Siglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket

et al. 2023

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Immunomodulatory Siglecs are controlled by their glycoprotein and glycolipid ligands. Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer, missing the complex behaviors of glycolipids in a membrane. Through optimizing a liposomal formulation to dissect Siglec–glycolipid interactions, it is shown that Siglec-6 can recognize glycolipids independent of its canonical binding pocket, suggesting that Siglec-6 possesses a secondary binding pocket tailored for recognizing glycolipids in a bilayer. A panel of synthetic neoglycolipids is used to probe the specificity of this glycolipid binding pocket on Siglec-6, leading to the development of a neoglycolipid with higher avidity for Siglec-6 compared to natural glycolipids. This neoglycolipid facilitates the delivery of liposomes to Siglec-6 on human mast cells, memory B-cells and placental syncytiotrophoblasts. A physiological relevance for glycolipid recognition by Siglec-6 is revealed for the binding and internalization of extracellular vesicles. These results demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane.

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Section: Discussionmentioning

confidence: 99%

Siglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket

et al. 2023

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“…Indeed, cell-bound GD2 and GD3 appear to be etiological to cancer onset or progression, lower the threshold for activation of receptor tyrosine kinases, and cause immune suppression allowing tumors to evade immune responses (14,16,17). Evidence that shed GD2 and GD3 are at least in part present in extracellular vesicles (ECVs) (46,47) raises the possibility that horizontal transmission or tissue homing of GD2/3 + -ECVs may play a role in these biological processes such as immune suppression.…”

Section: A Serum-based Elisa Quantifies Elevated Gd2 and Gd3 In Oc Pa...mentioning

confidence: 99%

GD2 and GD3 gangliosides as diagnostic biomarkers for all stages and subtypes of epithelial ovarian cancer

et al. 2023

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BackgroundOvarian cancer (OC) is the deadliest gynecological cancer, often diagnosed at advanced stages. A fast and accurate diagnostic method for early-stage OC is needed. The tumor marker gangliosides, GD2 and GD3, exhibit properties that make them ideal potential diagnostic biomarkers, but they have never before been quantified in OC. We investigated the diagnostic utility of GD2 and GD3 for diagnosis of all subtypes and stages of OC.MethodsThis retrospective study evaluated GD2 and GD3 expression in biobanked tissue and serum samples from patients with invasive epithelial OC, healthy donors, non-malignant gynecological conditions, and other cancers. GD2 and GD3 levels were evaluated in tissue samples by immunohistochemistry (n=299) and in two cohorts of serum samples by quantitative ELISA. A discovery cohort (n=379) showed feasibility of GD2 and GD3 quantitative ELISA for diagnosing OC, and a subsequent model cohort (n=200) was used to train and cross-validate a diagnostic model.ResultsGD2 and GD3 were expressed in tissues of all OC subtypes and FIGO stages but not in surrounding healthy tissue or other controls. In serum, GD2 and GD3 were elevated in patients with OC. A diagnostic model that included serum levels of GD2+GD3+age was superior to the standard of care (CA125, p<0.001) in diagnosing OC and early-stage (I/II) OC.ConclusionGD2 and GD3 expression was associated with high rates of selectivity and specificity for OC. A diagnostic model combining GD2 and GD3 quantification in serum had diagnostic power for all subtypes and all stages of OC, including early stage. Further research exploring the utility of GD2 and GD3 for diagnosis of OC is warranted.

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“…Some authors attribute the decrease of barrier functions of the epithelium in the transformation zone to the peculiarities of regenerative processes and the complexity of the process of restitution [14]. However, data on the distinctive properties of the barrier properties at the border of the epithelium, associated with the loading of pathogens in the exocervix and the "sterility" of the immunodeficient endocervix, are disputed at the present stage [1,7].…”

Section: Relevancementioning

confidence: 99%

Characteristics of the Quantitative Dynamics of Immunocompetent Cells in the Structure of the Cervix Epithelial Layer in Postmenopausal Women

Reva¹,

Yamamoto²,

Abramyan³

et al. 2022

ArveMED

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Malignancy in the cervix mucous membrane often develops in the junction zone of the ectocervix to the endocervix, which is the area of transformation of the stratified squamous epithelium into a single-layer cylindrical epithelium. The reasons for the insufficiency of immune protection in the transition zone of the epithelium from multilayer to single-layer cylindrical at the present stage do not have exhaustive explanations. Employing the method of immune histochemistry for the localization of immunocompetent cells identification was established by the dynamics of quantitative changes in CD-positive cells pool in the structure of cervix mucous membrane of women in the postmenopausal period from 1 to 5 years. A decrease in the number of CD-positive cells in all parts of the cervical mucous membrane was established in studied phenotypes: CD4, CD8, CD68, and CD163. Differences in the immune representation in the structure of the mucous membrane of the exocervix, the place of transition of the exocervix to the endocervix and endocervix were established. The reasons for the differences in the barrier protection of the epithelium, the authors associate with a greater microbial load of the exocervix, as well as relative immunodeficiency in comparison with other parts of the mucous membrane of the cervix, and an imbalance in the system for ensuring the plasticity of keratocytes in the transition zone of the exocervix to the endocervix with necrohormones and caylons.

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Structure and function of glycosphingolipids on small extracellular vesicles

Cited by 13 publications

References 89 publications

Siglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket

Siglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket

GD2 and GD3 gangliosides as diagnostic biomarkers for all stages and subtypes of epithelial ovarian cancer

Characteristics of the Quantitative Dynamics of Immunocompetent Cells in the Structure of the Cervix Epithelial Layer in Postmenopausal Women

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