Expression of functional E-selectin ligands on the plasma membrane of carcinoma cells correlates with poor prognosis in clear cell renal cell carcinoma

Tanio, Makoto; Muramoto, Akifumi; Hoshino, Hiroo; Murahashi, Masataka; Imamura, Yoshiaki; Yokoyama, Osamu; Kobayashi, Motohiro

doi:10.1016/j.urolonc.2021.02.013

Cited by 7 publications

(9 citation statements)

References 21 publications

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“…19 Membrane expression of respective KM93 and CA19-9 was scored as 0, 1+, 2+ or 3+, as described. 17,19 All tissue specimens were independently scored by the two authors of this article (M.T. and Y.F.)…”

Section: Methodsmentioning

confidence: 99%

“…We previously showed that expression of sLe x /sLe a correlated with poor prognosis in ccRCC using HECA-452 monoclonal antibody, which recognises both sLe x and sLe a . 17 Using KM93 and CA19-9 monoclonal antibodies, which specifically recognise sLe x and sLe a , respectively, we investigated whether sLe x and sLe a (quantified in this study by measurement of their membrane expression) could be proposed as prognostic biomarkers in ccRCC patients.…”

Section: Introductionmentioning

confidence: 99%

“…We previously showed that expression of sLe x /sLe a correlated with poor prognosis in ccRCC using HECA-452 monoclonal antibody, which recognises both sLe x and sLe a . 17…”

Section: Introductionmentioning

confidence: 99%

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Proposal of sialyl Lewis x/a as prognostic biomarkers in clear cell renal cell carcinoma: A study on a cohort of 117 patients submitted to curative surgery

Tanio

Fukiage

Muramoto

et al. 2022

Journal of Clinical Urology

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Objective: Metastatic recurrence has been reported to occur in 20–30% of patients with clear cell renal cell carcinoma (ccRCC). Although the prognosis of these patients is poor, no marker has been established to predict metastatic potential and/or prognosis. Therefore, we investigated membrane expression of sialyl Lewis x (sLex) and sialyl Lewis a (sLea), which is generally considered to be associated with cancer metastasis. Materials and methods: We enrolled 117 patients who underwent curative surgery for RCC and were pathologically diagnosed as ccRCC. Immunohistochemistry for sLex and sLea was performed to evaluate the signal intensity on the cell membrane. We statistically analysed whether membrane expression of sLex/sLea is correlated with clinicopathological parameters and prognosis. Results: Of the 117 patients, 72 were classified as sLex-positive and 44 as sLea-positive. The sLex-positive group had significantly shorter progression-free survival (PFS) and overall survival (OS) than the negative group. Similarly, the sLea-positive group had significantly shorter PFS than the negative group, and it showed a trend towards a reduction of OS, although it did not reach statistical significance, a fact that could be due to the small sample size. Conclusion: Both sLex and sLea could be possible future prognostic indicators in ccRCC. Level of evidence: Level 3

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proposal of sialyl Lewis x/a as prognostic biomarkers in clear cell renal cell carcinoma: A study on a cohort of 117 patients submitted to curative surgery

Tanio

Fukiage

Muramoto

et al. 2022

Journal of Clinical Urology

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“…E-selectin plays an important role in the process of inflammation by facilitating the adhesion and migration of immune cells to sites of inflammation [39]. Recent studies have shown that E-selectin may also be involved in cancer, since it was found to be upregulated in various types of cancer including breast [24,40], lung [41], and pancreatic cancer [42], and its expression levels are associated with more aggressive tumors and poorer prognosis in cancer patients [43].…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics Analyzes of Selectins Polymorphisms Reveal New Potential Cancer Biomarkers

Rabi¹,

Valente²,

Teixeira³

et al. 2023

Preprint

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Selectins are responsible for the early stages of cell migration as they control cell adhesion. They make the microenvironment permissive for metastatic events by promoting the activation of other cell adhesion molecules (CAMs). We employed several robust bioinformatics tools to evaluate gene sequence; single nucleotide polymorphisms (SNPs) in intronic and UTR regions; and missense SNPs with amino acid change in L-selectin (SELL), E-selectin (SELE), P-selectin (SELP) and PSGL-1 (SELPLG). We demonstrated that gene polymorphisms rs2229569, rs1131498, rs4987360, rs4987301 and rs2205849; polymorphisms rs3917777, rs2205894 and rs2205893 of SELP gene; rs7138370, rs7300972 and rs2228315 variants of SELPLG gene; and rs1534904 and rs5368 polymorphisms of SELE gene may produce important alterations in the DNA structure and consequent alterations in the morphology and function of the corresponding proteins. These Selectin polymorphic variants deserve further investigation in cancer patients, as they may become useful clinical markers for risk determination, diagnostic and prognostic biomarkers or even targets for targeted therapies.

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“…5 Under pathologic conditions, E-selectin also binds to sialyl Lewis a (sLe a , a structural isomer of sLe x also known as CA19-9), S i a α 2 → 3 G a l β 1 → 3 ( Fu c α 1 → 4 ) G l c N Ac β 1 → R , expressed on circulating tumor cells and can contribute to formation of hematogenous metastasis. 6 Taking advantage of this sLe x /sLe a -specific carbohydratebinding property of E-selectin, we previously used an E-selectin•IgM chimera, which is a soluble form of E-selectin, to functionally probe sLe x and/or sLe a in formalin-fixed, paraffin-embedded (FFPE) tissue sections of various human diseases, including chronic Helicobacter pylori gastritis, 7 ulcerative colitis, 8 testicular seminoma, 9 bladder urothelial carcinoma, 10 papillary thyroid carcinoma, 11 clear cell renal cell carcinoma, 12 and most recently, angioimmunoblastic T-cell lymphoma. 13 Immunohistological analysis of the E-selectin molecule itself, however, has been hampered by lack of E-selectin-specific monoclonal antibodies capable of staining FFPE tissue sections; thus researchers had no choice but to use frozen tissue sections.…”

Section: Introductionmentioning

confidence: 99%

Vascular E-selectin Expression Detected in Formalin-fixed, Paraffin-embedded Sections With an E-selectin Monoclonal Antibody Correlates With Ulcerative Colitis Activity

Murahashi¹,

Kogami²,

Muramoto³

et al. 2022

J Histochem Cytochem.

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It is widely accepted that E-selectin, an inducible endothelial cell adhesion molecule, plays a critical role in the initial step of neutrophil recruitment to sites of acute inflammation. However, immunohistological analysis of E-selectin has been hampered by lack of E-selectin-specific monoclonal antibodies that can stain formalin-fixed, paraffin-embedded (FFPE) tissue sections. Here, we employed E-selectin•IgM (a soluble form of E-selectin) as immunogen, and then, after negative selection with L-selectin•IgM and P-selectin•IgM and screening of FFPE sections of both COS-1 cells overexpressing E-selectin and acute appendicitis tissues, we successfully generated an E-selectin-specific monoclonal antibody capable of staining FFPE tissue sections. We used this antibody, designated U12-12, to perform quantitative immunohistological analysis of 390 colonic mucosal biopsy specimens representing ulcerative colitis. We found that the higher the histological disease activity, the greater the number of vessels expressing E-selectin, an observation consistent with previous analyses of frozen tissue sections. Furthermore, in active ulcerative colitis, E-selectin-expressing vessels contained neutrophils attached to endothelial cells, presumably in the process of extravasation, which eventually could cause epithelial damage. These results overall indicate that U12-12 is effective for E-selectin immunohistochemistry in archived FFPE samples representing various human diseases:

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Expression of functional E-selectin ligands on the plasma membrane of carcinoma cells correlates with poor prognosis in clear cell renal cell carcinoma

Cited by 7 publications

References 21 publications

Proposal of sialyl Lewis x/a as prognostic biomarkers in clear cell renal cell carcinoma: A study on a cohort of 117 patients submitted to curative surgery

Proposal of sialyl Lewis x/a as prognostic biomarkers in clear cell renal cell carcinoma: A study on a cohort of 117 patients submitted to curative surgery

Bioinformatics Analyzes of Selectins Polymorphisms Reveal New Potential Cancer Biomarkers

Vascular E-selectin Expression Detected in Formalin-fixed, Paraffin-embedded Sections With an E-selectin Monoclonal Antibody Correlates With Ulcerative Colitis Activity

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