Galectins bind to the N-glycan of FGFR1 and can directly activate the downstream signaling of FGFR1.

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.

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

T-antigen could be a biomarker of progression-free survival in patients with glioblastoma ?

A group from Department of Neurosurgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China has reported that T-antigen could be a biomarker of progression-free survival (PFS) in patients with glioblastoma (GMB).

They concluded from studies using Lectin microarrays that serum Jacalin-probed T-antigen levels, which were positively correlated with those in GBM tissues, may be used as a non-invasive biomarker of PFS, predicting GBM recurrences.

However, blog author thinks that their conclusion is problematic, because the glycan binding specificity of Jacalin is quite broad covering GlcNAcβ1-3GalNAc (Core3), Siaα2-3Galβ1-3GalNAc (sialyl T), Galβ1-3GalNAc (T-antigen), α-GalNAc (Tn-antigen), and also PNA could not discriminate glioblastoma so well, although it has high binding specificity to Galβ1-3GalNAc (T-antigen).

From the roles of galectins in epithelial-to-mesenchymal transition particulary in cancer

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.

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? ?

α2,3-sialylation is essential for melanoma growth and progression

A group from Department of Pathology, NYU Grossman School of Medicine, New York, USA etc. has reported about cganges in glycosylation of melanoma.

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.

Changes in glycosylation in Pancreatic Ductal Adenocarcinoma mediated by KRAS mutations

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.

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).

Sialic Acid is strong on Exosomes, but Why?

Glycans are said to be the face of cells, and the glycosylation on the cell surface changes depending on the tissue and desease state.
As a result, the glycosylation of exosomes released from cells drags the glycosylation of the cell surface, but for some reason, expression of sialic acid tends to be very strong.
For example, there is a paper written by Shimoda and Akiyoshi at. al., Kyoto University (see below).
Why is this?
There is a paper that says it may be aimed at masking the immune system (in Japanese), but is that true?
for example,
In contrast, the authors cited above suggest that it is involved in the uptake of exosomes via Siglecs on the cell surface.

(cited from the above listed paper)

Behind the “Cry for Help” response caused by plant pathogen infection

A group from State Key Laboratory of Efficient Utilization of Arid and Semi-arid Arable Land in Northern China, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, China, etc. has reported about how to induce “cry for help” response to assemble disease suppressing and growth promoting rhizomicrobiome.

The well-studied model pathogen Pseudomonas syringae pv. tomato (Pst) DC3000 and its nonpathogenic derivatives (D36E, D36EFLC and D36EHPM) were used in this experiment using Arabidopsis as a model plant.

Treatment with either DC3000 or the derivatives increased the relative contents of long chain organic acids (LCOAs) and amino acids in root exudates. The bacterial phyla Proteobacteria (32.1%–38.3%) and Actinobacteria (15.4%–20.7%) were the most abundant groups in the rhizosphere, and the genus Devosia (belonging to phylum Proteobacteria) was enriched in the D36E and D36EFLC treatments. Interestingly, the abundance of genus Devosia was negatively correlated with L-malic acid and myristic acid in root exudates but positively correlated with 4-hydroxypyridine.

Finally, it was shown that the metabolites of D36E and D36EFLC alone are sufficient to induce a “cry for help” response. So, this study demonstrates the ability of nonpathogenic strains and their MAMPs to act as elicitors to induce the formation of a disease-suppressive soil legacy, which can potentially support agricultural applications.

DC-SIGN recognizes the outer core oligosaccharide of LPS expressed on Gram-negative bacteria

Department of Chemical Science, University of Naples Federico II Via Cinthia 4, Naples, Italy, etc. has reported about molecular recognition of LPS by DC-SIGN.

Lipopolysaccharides (LPS) are peculiar glycolipids which represent the major components of the external leaflet of the gram-negative bacteria outer membrane. They consist of three structurally and genetically distinct domains: the lipid A, integrated in the outer membrane; the core oligosaccharide (OS), in turn composed of inner and outer core regions; and the distal O-specific polysaccharide (O-PS) chain, that extends outwards the bacterial surface

Structurally speaking, it is a dodecasaccharide composed of two residues of galactose and three glucose units in the outer core region and three L-glycero-D-manno-heptoses and two 3-deoxy-D-manno-oct-2-ulosonic acids (Kdo), in the inner core portion; the two glucosamine residues at reducing end belong to the lipid A moiety.

One of the main representatives of transmembrane C-type lectins is DC-SIGN also known as CD209. This lectin is found on macrophages, monocytes, and is mainly expressed by dendritic cells which act as potent phagocytic cells, and it is know that DC-SIGN belongs to the mannose receptor family. On the other hand, it has been shown that the DC-SIGN induced phagocytosis of E. coli occurs in the absence of O-antigen polysaccharides, and in the presence of a complete core OS.

In this study, it was found that DC-SIGN binds to the outer core pentasaccharide (composed of two residues of galactose and three glucose units), which acts as a crosslinker between two different tetrameric units of DC-SIGN.

VVA Lectin characteristically binds to invasive urothelial carcinomas

A group from Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan, etc. has reported about characteristic glycan marker in invasive urothelial carcinomas.

The study found that a specific lectin, VVL, was present in cases of invasive urothelial carcinoma and its variant components. More intense VVL staining was observed with invasive or muscle invasive urothelial carcinomas and urothelial carcinomas with variant components than that in non-invasive urothelial carcinomas

VVL recognizes the GalNAc residue linked to serine or threonine in a polypeptide Tn antigen. Other glycan structures, such as Galβ1,3GalNAc-α-Ser/Thr (T antigen) and GlcNAcα1,6-GalNAc-α-Ser/Thr, including terminal α1,4- and β1,4-linked GalNAc, were also recognized by VVL, but with a weaker affinity.

VVA will have the potential to serve as a promising target for drug delivery in future clinical studies.

Changes in glycan composition of EPS produced by bacteria in aerobic granular sludge used in wastewater treatment processes

A group from Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands, etc. has reported about changes of glycan composition in aerobic granular sludge by using lectin microarray and GC-MS etc.

Aerobic granular sludge is a community of microbial organisms that remove carbon, nitrogen, phosphorus and other pollutants in a single sludge system used for wastewater treatments. In this research, the dynamic changes of the glycan profile of a few extracellular polymeric substance (EPS) samples extracted from aerobic granular sludge were monitored by GC-MS and lectin microarray.

EPSs were collected at different stages during its adaptation to the seawater condition on the initial day, 18th, and 30th days after the start of the reactor (denoted as EPSt0, EPSt18, and EPSt30 hereafter).

The application of the lectin microarray confirmed the presence of glycoproteins and effectively monitored its alteration along the adaptation to the seawater condition. Additionally, the result of lectin microarray is in line with the results of other analyses performed by GC-MS etc. This suggests that the lectin microarray is a successful platform for high-throughput glycan profiling of glycoproteins in microbial aggregates such as granular sludge.

Interestingly, there were more glycoproteins in EPSt18 than EPSt0 and EPSt30, and the glycosylation pattern of EPSt18 is significantly diverse. This indicates that, in response to the environmental change, i.e., exposure to the increased salt condition, one of the adaptation strategies of the microorganisms can be altering the glycosylation of proteins in quantity and diversity.

p.s., Her collaborator, Dr. Tateno in AIST, is also our collaborator regarding a glycan profiling system using lectin microarrays and an evanescent-filed fluorescence excitation scanner, GlycoStation.