Rho family small GTPase Rif regulates Wnt5a-Ror1-Dvl2 signaling and promotes lung adenocarcinoma progression.

Rho in filopodia (Rif), a member of the Rho family of small GTPases, induces filopodia formation primarily on the dorsal surface of cells; however, its function remains largely unclear. Here, we show that Rif interacts with Ror1, a receptor for Wnt5a that can also induce dorsal filopodia. Our immunohistochemical analysis revealed a high frequency of coexpression of Ror1 and Rif in lung adenocarcinoma.

Correction: Hoshi et al. High Correlation among Brain-Derived Major Protein Levels in Cerebrospinal Fluid: Implication for Amyloid-Beta and Tau Protein Changes in Alzheimer's Disease. 2022, , 355.

In the original publication [...

Brain-Derived Major Glycoproteins Are Possible Biomarkers for Altered Metabolism of Cerebrospinal Fluid in Neurological Diseases.

Cerebrospinal fluid (CSF) plays an important role in the homeostasis of the brain. We previously reported that CSF major glycoproteins are biosynthesized in the brain, i.e.

Expression of Transferrin Protein and Messenger RNA in Neural Cells from Mouse and Human Brain Tissue.

Iron is an essential nutrient in the body. However, iron generates oxidative stress and hence needs to be bound to carrier proteins such as the glycoprotein transferrin (Tf) in body fluids. We previously reported that cerebrospinal fluid contains Tf glycan-isoforms that are derived from the brain, but their origins at the cellular level in the brain have not yet been elucidated.

High Correlation among Brain-Derived Major Protein Levels in Cerebrospinal Fluid: Implication for Amyloid-Beta and Tau Protein Changes in Alzheimer's Disease.

The cerebrospinal fluid (CSF) plays an important role in homeostasis of the brain. We previously demonstrated that major CSF proteins such as lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin (Tf) that are biosynthesized in the brain could be biomarkers of altered CSF production. Here we report that the levels of these brain-derived CSF proteins correlated well with each other across various neurodegenerative diseases, including Alzheimer's disease (AD).

Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer's Disease.

Glycosylation is a cell type-specific post-translational modification that can be used for biomarker identification in various diseases. Aim of this study is to explore glycan-biomarkers on transferrin (Tf) for Alzheimer's disease (AD) in cerebrospinal fluid (CSF). Glycan structures of CSF Tf were analyzed by ultra-performance liquid chromatography followed by mass spectrometry.

Soluble protein tyrosine phosphatase receptor type Z (PTPRZ) in cerebrospinal fluid is a potential diagnostic marker for glioma.

Background: High-grade glioma is the most pervasive and lethal of all brain malignancies. Despite advances in imaging technologies, discriminating between gliomas and other brain diseases such as multiple sclerosis (MS) often requires brain biopsy. Several reports show that protein tyrosine phosphatase receptor Z (PTPRZ) is highly expressed in glioblastoma, and we found that a soluble cleaved form of PTPRZ (sPTPRZ) was present in the cerebrospinal fluid (CSF).

Glycoform-Specific Visualization in Immunohistochemistry by "Lectin Inhibition".

Antibodies are useful for localizing glycoprotein antigens in histochemistry, but they do not differentiate glycoforms in tissue sections because conventional antibodies recognize only protein epitopes rather than glycans. Glycan epitopes are recognized by lectins, which are found, occasionally, to inhibit antigen-antibody reaction in a glycoform-specific manner (lectin inhibition). Here we describe the application of lectin inhibition to immunohistochemistry for visualizing a glycoform in a tissue section.

Simple and Rapid Detection of Glycoforms by "Lectin Inhibition" Assay.

Glycoforms are otherwise identical proteins with different glycosylation. A lectin, Sambucus sieboldiana agglutinin (SSA), specifically binds glycoforms having α2,6-sialyl residues. The binding is found to inhibit antigen-antibody reaction; e.

Mesenchymal stem cell-derived CXCL16 promotes progression of gastric cancer cells by STAT3-mediated expression of Ror1.

Bone marrow-derived mesenchymal stem or stromal cells (MSC) have been shown to be recruited to various types of tumor tissues, where they interact with tumor cells to promote their proliferation, survival, invasion and metastasis, depending on the type of the tumor. We have previously shown that Ror2 receptor tyrosine kinase and its ligand, Wnt5a, are expressed in MSC, and Wnt5a-Ror2 signaling in MSC induces expression of CXCL16, which, in turn, promotes proliferation of co-cultured MKN45 gastric cancer cells via the CXCL16-CXCR6 axis. However, it remains unclear how CXCL16 regulates proliferation of MKN45 cells.

Ratio of Alpha 2-Macroglobulin Levels in Cerebrospinal Fluid and Serum: An Expression of Neuroinflammation in Acute Disseminated Encephalomyelitis.

Background: Acute encephalitis and encephalopathy are life-threatening diseases in children. However, no laboratory examinations are performed for their early diagnosis and treatment. Alpha 2-macroglobulin (α2M) is a blood glycoprotein that increases during the early stages of inflammation.

Lectin-Based Assay for Glycoform-Specific Detection of α2,6-sialylated Transferrin and Carcinoembryonic Antigen in Tissue and Body Fluid.

Antibodies are useful for detecting glycoprotein antigens, but a conventional antibody recognizes only a protein epitope rather than a glycan. Thus, glycan isoform detection generally requires time- and labor-consuming processes such as lectin affinity column chromatography followed by sandwich ELISA. We recently found antigen-antibody reactions that were inhibited by lectin binding to glycans on the glycoprotein antigen, leading to a convenient glycoform-specific assay.

Rapid increase of 'brain-type' transferrin in cerebrospinal fluid after shunt surgery for idiopathic normal pressure hydrocephalus: a prognosis marker for cognitive recovery.

Idiopathic normal pressure hydrocephalus (iNPH) is a dementia-inducing disorder. Primary cause of iNPH is speculated to be a reduction of cerebrospinal fluid (CSF) absorption, which secondarily induces hydrocephalus, compression of brain, and reduction of CSF production. Patients are treated by surgically inserting a shunt to deliver excess CSF to the abdominal cavity.

Spontaneous intracranial hypotension is diagnosed by a combination of lipocalin-type prostaglandin D synthase and brain-type transferrin in cerebrospinal fluid.

Background: Spontaneous intracranial hypotension (SIH) is caused by cerebrospinal fluid (CSF) leakage. Definitive diagnosis can be difficult by clinical examinations and imaging studies.

Methods: SIH was diagnosed with the following criteria: (i) evidence of CSF leakage by cranial magnetic resonance imaging (MRI) findings of intracranial hypotension and/or low CSF opening pressure; (ii) no recent history of dural puncture.

Evaluation of blood-brain barrier function by quotient alpha2 macroglobulin and its relationship with interleukin-6 and complement component 3 levels in neuropsychiatric systemic lupus erythematosus.

Although quotient of alpha2 macroglobulin (Qα2MG) was previously reported to be useful for the evaluation of blood-brain barrier (BBB) function, it is not commonly used. We therefore evaluated BBB function among the various subsets of neuropsychiatric systemic lupus erythematosus (NPSLE) using quotient Q α2MG. Furthermore, we determined the correlation between Q α2MG and cerebrospinal (CSF) interleukin (IL)-6 level and quotient complement component 3 (Q C3).

A unique glycan-isoform of transferrin in cerebrospinal fluid: A potential diagnostic marker for neurological diseases.

Background: Cerebrospinal fluid (CSF) is sequestered from blood by the blood-brain barrier and directly communicates with brain parenchymal interstitial fluid, leading to contain specific biomarkers of neurological diseases.

Scope Of Review: CSF contains glycan isoforms of transferrin (Tf): one appears to be derived from the brain and the other from blood.

Major Conclusions: CSF contains two glycan-isoforms; brain-type Tf and serum-type Tf.

Subgroup differences in 'brain-type' transferrin and α-synuclein in Parkinson's disease and multiple system atrophy.

Two transferrin (Tf) glycan-isoforms were previously found in cerebrospinal fluid (CSF); one appears to be derived from serum (Tf-2) and the other from choroid plexus, a CSF-producing tissue (Tf-1). To analyse metabolic differences associated with the two isoforms, their ratio (Tf-2/Tf-1) was defined as the Tf index. Here we report that Tf indices of patients with tauopathies including Alzheimer's disease (2.

In situ visualization of a glycoform of transferrin: localization of α2,6-sialylated transferrin in the liver.

We previously found that a lectin, Sambucus sieboldiana agglutinin (SSA), bound to α2,6-sialylated glycan epitopes on transferrin and inhibited anti-transferrin antibody binding to the antigen in ELISA (SSA inhibition). Here we report that SSA inhibition is applicable to immunohistochemistry, localizing α2,6-sialylated transferrin in the liver. Immunohistochemistry using anti-transferrin polyclonal antibody revealed that transferrin was detected in hepatocytes near interlobular veins.

Lectin-dependent inhibition of antigen-antibody reaction: application for measuring α2,6-sialylated glycoforms of transferrin.

We developed a high-throughput Enzyme-linked immunosorbent assay (ELISA) for measuring α2,6-sialylated transferrin (Tf), based on inhibition of anti-Tf antibody binding to α2,6-sialylated Tf by a lectin, Sambucus sieboldiana Agglutinin (SSA). The inhibition was not observed with other glycoforms, such as periodate-treated, sialidase-treated and sialidase/galactosidase-treated Tf, suggesting that the assay was glycoform specific. This finding was applied to an automated latex-agglutination immunoassay, using SSA lectin as an inhibitor (SSA-ALI).

High Throughput ELISAs to Measure a Unique Glycan on Transferrin in Cerebrospinal Fluid: A Possible Extension toward Alzheimer's Disease Biomarker Development.

We have established high-throughput lectin-antibody ELISAs to measure different glycans on transferrin (Tf) in cerebrospinal fluid (CSF) using lectins and an anti-transferrin antibody (TfAb). Lectin blot and precipitation analysis of CSF revealed that PVL (Psathyrella velutina lectin) bound an unique N-acetylglucosamine-terminated N-glycans on "CSF-type" Tf whereas SSA (Sambucus sieboldiana agglutinin) bound α2,6-N-acetylneuraminic acid-terminated N-glycans on "serum-type" Tf. PVL-TfAb ELISA of 0.

A unique N-glycan on human transferrin in CSF: a possible biomarker for iNPH.

Idiopathic normal pressure hydrocephalus (iNPH) is an elderly dementia caused by abnormal metabolism in the cerebrospinal fluid (CSF). The tap test is the current basis for confirming iNPH, but it shows very low sensitivity, indicating that many patients who might be cured by a shunt operation will be missed. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we found two transferrin isoforms: one had a unique N-glycan (Tf-1) whereas the other had N-glycan similar to that of serum transferrin (Tf-2).