Serum sialyl Lewis X-i antigen in lung adenocarcinoma and idiopathic pulmonary fibrosis

Satoh, Hiroaki

doi:10.1136/thorax.57.3.263

Cited by 8 publications

(6 citation statements)

References 23 publications

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“…The present study showed that sLe x /sLe a glycans are significantly overexpressed in NSCLC tissues in comparison with matched normal lung tissues. These results are in agreement with previous studies showing increased expression of sLe x /sLe a glycans in both serum and biopsies from patients with NSCLC (14,42,47). The data also showed that NSCLC has high reactivity with E-selectin compared with normal tissue, whose intensity is correlated with anti-sLe x /sLe a mAb reactivity.…”

Section: Discussionsupporting

confidence: 93%

Carcinoembryonic antigen is a sialyl Lewis x/a carrier and an E‑selectin ligand in non‑small cell lung cancer

et al. 2019

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The formation of distant metastasis resulting from vascular dissemination is one of the leading causes of mortality in non-small cell lung cancer (NSCLC). This metastatic dissemination initiates with the adhesion of circulating cancer cells to the endothelium. The minimal requirement for the binding of leukocytes to endothelial E-selectins and subsequent transmigration is the epitope of the fucosylated glycan, sialyl Lewis x (sLex), attached to specific cell surface glycoproteins. sLex and its isomer sialyl Lewis a (sLea) have been described in NSCLC, but their functional role in cancer cell adhesion to endothelium is still poorly understood. In this study, it was hypothesised that, similarly to leukocytes, sLe glycans play a role in NSCLC cell adhesion to E-selectins. To assess this, paired tumour and normal lung tissue samples from 18 NSCLC patients were analyzed. Immunoblotting and immunohisto-chemistry assays demonstrated that tumour tissues exhibited significantly stronger reactivity with anti-sLex/sLea antibody and E-selectin chimera than normal tissues (2.2- and 1.8-fold higher, respectively), as well as a higher immunoreactive score. High sLex/sLea expression was associated with bone metastasis. The overall α1,3-fucosyltransferase (FUT) activity was increased in tumour tissues, along with the mRNA levels of FUT3, FUT6 and FUT7, whereas FUT4 mRNA expression was decreased. The expression of E-selectin ligands exhibited a weak but significant correlation with the FUT3/FUT4 and FUT7/FUT4 ratios. Additionally, carcinoembryonic antigen (CEA) was identified in only 8 of the 18 tumour tissues; CEA-positive tissues exhibited significantly increased sLex/sLea expression. Tumour tissue areas expressing CEA also expressed sLex/sLea and showed reactivity to E-selectin. Blot rolling assays further demonstrated that CEA immunoprecipitates exhibited sustained adhesive interactions with E-selectin-expressing cells, suggesting CEA acts as a functional protein scaffold for E-selectin ligands in NSCLC. In conclusion, this work provides the first demonstration that sLex/sLea are increased in primary NSCLC due to increased α1,3-FUT activity. sLex/sLea is carried by CEA and confers the ability for NSCLC cells to bind E-selectins, and is potentially associated with bone metastasis. This study contributes to identifying potential future diagnostic/prognostic biomarkers and therapeutic targets for lung cancer.

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Section: Discussionsupporting

confidence: 93%

Carcinoembryonic antigen is a sialyl Lewis x/a carrier and an E‑selectin ligand in non‑small cell lung cancer

et al. 2019

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“…They plotted ROC curves and demonstrated a clear superiority in terms of specificity, sensitivity and diagnostic accuracy of KL-6 plasma levels in discriminating interstitial pneumonia from alveolar pneumonia and healthy volunteers. In another study, Satoh et al [72] coupled SLX serum cut-off levels with Western blotting analysis and documented that this combination is of high diagnostic power in differentiating IPF from lung adenocarcinoma.…”

Section: Serum Biomarkers In Idiopathic Pulmonary Fibrosis and Colmentioning

confidence: 99%

Serum biomarkers in interstitial lung diseases

et al. 2005

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The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to interstitial lung diseases (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in interstitial lung diseases and their potential value as prognostic and diagnostic tools and present some of the future perspectives and challenges.

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“…An increased level of immunoglobulin in bronchial washings was considered to be specifically related to lung cancer [14,15]. Aberrant sialylation of glycoconjugates in sera of patients with lung adenocarcinoma was reported earlier [10]. The present study reports the detection of disease specific sialoglycoconjugate specific antibodies in the BALF of NSCLC patients.…”

Section: Introductionmentioning

confidence: 52%

“…Several carbohydrate specific monoclonal antibodies of IgM and IgG type were developed, which could discriminate among various tumors and normal tissues [8]. Lung adenocarcinoma is known to be one of the abundant sources of Lewis-x and the related antigens and many murine monoclonal antibodies directed to lung cancer cells were shown to recognize these antigens [9,10]. Furthermore, the presence of antibodies against the disease specific glycoconjugates has also been detected in the sera of cancer patients [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Detection of disease specific sialoglycoconjugate specific antibodies in bronchoalveolar lavage fluid of non-small cell lung cancer patients

et al. 2010

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In this study, we report the presence of significantly higher level of GM3 specific IgG antibodies (IgG(TL)) in the bronchoalveolar lavage fluid obtained from tumor bearing lung of non-small cell lung cancer (NSCLC) patients as compared to other non-neoplastic controls. The antibodies were isolated using DEAE-cellulose anion exchange chromatography and molecular weight of the subunits of IgG(TL) was confirmed in SDS-PAGE. IgG(TL) revealed high specificity to GM3 and the IgG distribution was confined to IgG1. Furthermore, IgG(TL) showed strong reactivity with NSCLC cell lines as well as the tissue biopsies and cells obtained from fine needle aspirations of NSCLC patients. A 66 kDa membrane glycoprotein of NSCLC cell lines was found to interact specifically with IgG(TL), the intensity of which was drastically reduced in presence of GM3. Further, binding of Maackia amurensis agglutinin [specific for NeuAcalpha(2-->3)Gal unit , the same disaccharide unit also known to be present in GM3] to the 66 kDa band confirmed it to be a sialoglycoprotein in nature. IgG(TL) could not show any reactivity to alkaline borohydrate treated or periodate oxidised membrane fractions, suggesting the probable involvement of the carbohydrate moiety of the 66 kDa glycoprotein in the interaction with IgG(TL). Thus, the 66 kDa sialoglycoprotein seems to be the NSCLC specific sialoglycoconjugate. Taken together, IgG(TL) antibodies may have the potential to serve as a unique probe for detail investigation of NSCLC specific cell surface sialoglycoconjugate. Further, due to high specificity of IgG(TL) to GM3, it may be possible to develop a simple alternative diagnostic approach (GM3-ELISA) for NSCLC.

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Serum sialyl Lewis X-i antigen in lung adenocarcinoma and idiopathic pulmonary fibrosis

Cited by 8 publications

References 23 publications

Carcinoembryonic antigen is a sialyl Lewis x/a carrier and an E‑selectin ligand in non‑small cell lung cancer

Carcinoembryonic antigen is a sialyl Lewis x/a carrier and an E‑selectin ligand in non‑small cell lung cancer

Serum biomarkers in interstitial lung diseases

Detection of disease specific sialoglycoconjugate specific antibodies in bronchoalveolar lavage fluid of non-small cell lung cancer patients

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