Category: Nature

A group from Shenzhen Key Laboratory of Metabolic Health, Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, China has reported about roles of glycan and lectin interactions in embryo attachment.
https://www.sciencedirect.com/science/article/pii/S2090123224003060?via%3Dihub

Althopugh the interaction between trophoblastic L-selectin and endometrial sLeX has been reported as a glycosylation-dependent adhesion mechanism underlying embryo implantation, it was also found that Siglec-6 expressed in the trophectoderm of human embryos play a key role in facilitating embryo attachment via recognizing the sTn-covered receptive endometrium.

A group from Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China has reported about changes in IgG glycosylation patterns for antiphospholipid syndrome (APS) patients with lectin microarray.
https://onlinelibrary.wiley.com/doi/10.1111/sji.13366

It was found that IgG complexes from APS patients exhibited a significantly elevated exposure of GalNAc residues compared with healthy controls and disease controls. This suggests that elevated GalNAc on IgG plays a role in the progression of APS. However, compared with N-linked glycosylation, the effects of O-glycosylation on IgG structure and function remain to be elucidated.

A group from Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia has reported about surface glycans of Microvesicles derived from endothelial Ccells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11171894/

As shown below, it is clearly shown that the surface glycans of MVs are dominated by α2-6-sialylated forms as N-glycans and the level of some Man-containing glycans are significantly decreased in MVs, comparing surface glycans of MVs and those of Cells.

A group from Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland has reported that galectin-1, -7, and -8 can activate FGFR1 signaling and control endocytosis.
https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01661-3

N-glycans of FGFR1 are recognized by extracellular galectins (Gal-1, Gal-7, and Gal-8), which are not authentific ligand of FGFR1 (i.e., FGF1), and the binding of those galectins to FGFR1 trigers activation of the receptor and initiation of downstream signaling cascades. Subsequent endocytosis of activated FGFR1 serves as a major cellular mechanism for the downregulation of FGFR1 signaling.

Both FGF1 and Gal-1 directly activate FGFR1 and after short and intensive pulse of FGFR1 signaling, the receptor is shut down due to the induction of clathrin medited endocytosis, followed by lysosomal degradation of the receptor. Gal-7 and -8 also directly activate FGFR1 by the receptor clustering mechanism, but by inhibiting FGFR1 endocytosis and degradation, these galectins largely prolong FGFR1 signaling.

pFGFR means tyrosine-phosphorylated FGFR1

I have read a review article on the epithelial-to-mesenchymal transition (EMT) of galectins written by the groups of CEBICEM, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile, and others. The following is the typical phrases extracted from this review.
https://biolres.biomedcentral.com/articles/10.1186/s40659-024-00490-5

In gastric cancer, increased levels of Gal-1 have been associated with lower overall and disease-free survival, as well as with an increased incidence of lymph node metastasis in patients. Gastric cancer cell lines produce Gal-1, which promotes EMT and increases proliferation, invasion and metastatic potential of these cells. In ovarian cancer, serum samples show that Gal-1 levels are increased and correlate with a higher histological grade and lymph node metastasis. In ovarian cancer cell lines, Gal-1 overexpression promotes EMT and increases cell migration and invasion through the activation of the MAPK-JNK/p38 signaling pathway, while silencing of Gal-1 has opposite effects. High levels of Gal-1 are detected in stromal cells from gastric cancer and pancreatic ductal adenocarcinoma tumors in correlation with an EMT phenotype of carcinoma cells. Gal-1-overexpression in pancreatic stellate cells (PSC) induces EMT in co-cultured pancreatic carcinoma cells, enhancing their proliferation and invasion through the NF-κB pathway. Downregulation of Gal-3 expression reduces tumor growth in xenograft colon cancer models whereas its overexpression enhances the metastatic potential of cancer cells. In breast, colon, and prostate cancer cell lines exogenously added Gal-3 promotes EMT by its interaction with Trop-2, a highly-glycosylated membrane protein involved in cancer progression. Gal-4 has been reported in human prostate cancer tissues with expression levels correlating with metastasis and poor patient survival. Gal-8 is a widely expressed galectin in human tissues and carcinomas and has been associated with an unfavorable prognosis in various types of cancer. Gal-8 contributes to cancer progression and metastasis by regulating the production of immunoregulatory cytokines, thereby facilitating the recruitment of cancer cells to metastatic sites.

In other words, different types of galectins are involved in cancer in various places, but I think the issue is the degree of the contribution of galectin involvement. Glycans and lectins basically play regulatory roles except for innate immunity and congenital disorder of glycosylation (CDG).

Therefore, when trying to cure disease from a view point of glycans and lectins, I think it is necessary to narrow down the disease to those in which these are involved with higher contributions.
What do you think? ?

A group from Department of Pathology, NYU Grossman School of Medicine, New York, USA etc. has reported about cganges in glycosylation of melanoma.
https://www.biorxiv.org/content/10.1101/2024.03.08.584072v1.full.pdf

It has shown using lectin microarrays that α1,2 fucose decreased in primary melanoma compared to nevi.
Interestingly, core fucose was high in nevi and lower in primary melanoma but then regained in metastatic melanoma.
It was also observed that 2,3 syalylation increased significantly in both primary and metastatic melanoma compared to nevi.

A group from Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Japan, etc. has reported about changes in glycosylation in Pancreatic Ductal Adenocarcinoma mediated by KRAS gene mutations.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10963106/

It was shown that Fucosilation and mannosylation were upregurated in pancreatin ductal adenocarcinoma with KRAS gene mutations.
The lectins enriched in KRAS mutants included fucose-binding lectins (AAL, rAAL, AOL, rAOL, rRSIIL, and UEAI) and mannose-binding lectins (rRSL, rBC2LCA, rPAIIL, and NPA).