Integrins αvβ6, α6β4 and α3β1 are down‐regulated in cholangiolocellular carcinoma but not cholangiocarcinoma

Soejima, Yurie; Inoue, Masafumi; Takahashi, Yoshihisa; Uozaki, Hiroshi; Sawabe, Motoji; Fukusato, Toshio

doi:10.1111/hepr.12312

Cited by 16 publications

(24 citation statements)

References 34 publications

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“…Soejima et al indicated the downregulation of αvβ6, α6β4 and α3β1 integrins in CoCC and its respectively high expression in CCC. These findings suggest the use of integrins as a diagnostic tool in the differential diagnosis of CoCC and CCC [13]. These findings are also supported by earlier studies demonstrating that αvβ6 integrin is a promising marker of CCC, but not HCC as the expression levels were very different in these tumors [14].…”

supporting

confidence: 81%

“…In this study, Soejima et al evaluated integrin expression and immunolocalization of the extracellular matrix proteins in cholangiolocellular carcinoma (CoCC), CCC, hepatocellular carcinoma (HCC) and classical type combined hepatocellular CCCs. Samples were collected and immunostained for β6, β4 and α3 integrins, fibronectin and laminin [13]. Little or no positivity for β6, β4 and α3 integrins were shown in the CoCC and HCC specimens.…”

mentioning

confidence: 99%

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Our Panel of Experts Highlight the Most Important Research Articles Across the Spectrum of Topics Relevant to the Field of Hepatic Oncology

Owens

Francis

2015

Hepat. Oncol.

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supporting

confidence: 81%

mentioning

confidence: 99%

Our Panel of Experts Highlight the Most Important Research Articles Across the Spectrum of Topics Relevant to the Field of Hepatic Oncology

Owens

Francis

2015

Hepat. Oncol.

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“…The genes that were simultaneously presented in the extracellular matrix-receptor pathway and were revealed to be ASGs, included chondroadherin (CHAD), integrin subunit (ITG)-A3, ITG-B1 and laminin subunit alpha-5 (LAMA5). Three of the aforementioned genes, (ITGA3, ITGB1 and LAMA5) have previously been demonstrated to be associated with the progression of ICC (25,26). CHAD encodes a cartilage matrix protein, which may mediate adhesion of isolated chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers of intrahepatic cholangiocarcinoma via integrated analysis of mRNA and miRNA microarray data

Chang

Liu

et al. 2017

Molecular Medicine Reports

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The present study aimed to identify potential therapeutic targets of intrahepatic cholangiocarcinoma (ICC) via integrated analysis of gene (transcript version) and microRNA (miRNA/miR) expression. The miRNA microarray dataset GSE32957 contained miRNA expression data from 16 ICC, 7 mixed type of combined hepatocellular-cholangiocarcinoma (CHC), 2 hepatic adenoma, 3 focal nodular hyperplasia (FNH) and 5 healthy liver tissue samples, and 2 cholangiocarcinoma cell lines. In addition, the mRNA microarray dataset GSE32879 contained mRNA expression data from 16 ICC, 7 CHC, 2 hepatic adenoma, 5 FNH and 7 healthy liver tissue samples. The datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEMs) in ICC samples compared with healthy liver tissues were identified via the limma package, following data preprocessing. Genes that exhibited alternative splicing (AS) in ICC samples were identified via AltAnalyze software. Functional enrichment analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis. Target genes of DEMs were identified using the TargetScan database. The regulatory association between DEMs and any overlaps among DEGs, alternative splicing genes (ASGs) and target genes of DEMs were retrieved, and a network was visualized using the Cytoscape software. A total of 2,327 DEGs, 70 DEMs and 623 ASGs were obtained. Functional enrichment analysis indicated that DEGs were primarily enriched in biological processes and pathways associated with cell activity or the immune system. A total of 63 overlaps were obtained among DEGs, ASGs and target genes of DEMs, and a regulation network that contained 243 miRNA-gene regulation pairs was constructed between these overlaps and DEMs. The overlapped genes, including sprouty-related EVH1 domain containing 1, protein phosphate 1 regulatory subunit 12A, chromosome 20 open reading frame 194, and DEMs, including hsa-miR-96, hsa-miR-1 and hsa-miR-25, may be potential therapeutic targets for the future treatment of ICC.

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“…Integrin a1b1 has been shown to be involved in the attachment to collagen IV and laminins containing the a4 subunit, 30,60 while a3b1, a6b1, and a6b4 have all been shown to interact specifically with laminins. [60][61][62] aVb5, aVb1, and a5b1 along with several other integrin heterodimers have been shown to interact with RGD sequences from varying ECM proteins, including collagen I, fibronectin, and vitronectin. 30,35,63 The increase of each of these subunits in adipogenically differentiated cultures, along with increases in ECM proteins that they are able to interact with, supports the hypothesis that these integrins may be important to the differentiation process.…”

Section: Discussionmentioning

confidence: 99%

Vitronectin-Based, Biomimetic Encapsulating Hydrogel Scaffolds Support Adipogenesis of Adipose Stem Cells

Clevenger

Hinman

Rubin

et al. 2016

Tissue Engineering Part A

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Soft tissue defects are relatively common, yet currently used reconstructive treatments have varying success rates, and serious potential complications such as unpredictable volume loss and reabsorption. Human adipose-derived stem cells (ASCs), isolated from liposuction aspirate have great potential for use in soft tissue regeneration, especially when combined with a supportive scaffold. To design scaffolds that promote differentiation of these cells down an adipogenic lineage, we characterized changes in the surrounding extracellular environment during adipogenic differentiation. We found expression changes in both extracellular matrix proteins, including increases in expression of collagen-IV and vitronectin, as well as changes in the integrin expression profile, with an increase in expression of integrins such as aVb5 and a1b1. These integrins are known to specifically interact with vitronectin and collagen-IV, respectively, through binding to an Arg-Gly-Asp (RGD) sequence. When three different short RGD-containing peptides were incorporated into three-dimensional (3D) hydrogel cultures, it was found that an RGD-containing peptide derived from vitronectin provided strong initial attachment, maintained the desired morphology, and created optimal conditions for in vitro 3D adipogenic differentiation of ASCs. These results describe a simple, nontoxic encapsulating scaffold, capable of supporting the survival and desired differentiation of ASCs for the treatment of soft tissue defects.

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Integrins αvβ6, α6β4 and α3β1 are down‐regulated in cholangiolocellular carcinoma but not cholangiocarcinoma

Cited by 16 publications

References 34 publications

Our Panel of Experts Highlight the Most Important Research Articles Across the Spectrum of Topics Relevant to the Field of Hepatic Oncology

Our Panel of Experts Highlight the Most Important Research Articles Across the Spectrum of Topics Relevant to the Field of Hepatic Oncology

Identification of biomarkers of intrahepatic cholangiocarcinoma via integrated analysis of mRNA and miRNA microarray data

Vitronectin-Based, Biomimetic Encapsulating Hydrogel Scaffolds Support Adipogenesis of Adipose Stem Cells

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