Immunoprofiles of 11 Biomarkers Using Tissue Microarrays Identify Prognostic Subgroups in Colorectal Cancer

Knösel, Thomas; Emde, Anna; Schlüns, Karsten; Yuan, Chen; Jürchott, Karsten; Krause, Matthias; Dietel, Manfred; Petersen, Iver

doi:10.1593/neo.05178

Cited by 76 publications

(62 citation statements)

References 32 publications

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“…The "overexpression" of ADAM10 in MCL tumors per se may be biologically important, because one previous report showed that overexpression of ADAM10 in colorectal cancer was significantly correlated with a higher clinical stage. 16 In this study, we demonstrated that 5 of 5 cases of MCL showing ADAM10 immunoreactivity also expressed the active/mature form of ADAM10. It is likely that most MCL tumors overexpress ADAM10 and carry constitutive activation of this protein.…”

Section: Adam10 Inhibition Enhanced the Growth-suppressing Effect Of supporting

confidence: 49%

“…15 In another study, ADAM10 expression detectable by immunohistochemistry in colorectal cancer patient samples was found to be correlated with a higher clinical stage. 16 Using immunohistochemistry, it was also found that ADAM10 is overexpressed in squamous cell carcinomas of the oral cavity compared with the benign epithelial cells; knockdown of ADAM10 expression using short interfering RNA (siRNA) in the cell lines derived from these tumors was shown to induce a significant decrease in cell growth. 17 Similar findings were made in pancreatic cancer, in which inhibition of ADAM10 expression in pancreatic carcinoma cell lines resulted in a significant decrease in invasiveness and migration.…”

Section: Introductionmentioning

confidence: 99%

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Constitutive activation of metalloproteinase ADAM10 in mantle cell lymphoma promotes cell growth and activates the TNFα/NFκB pathway

Armanious¹,

Gélébart²,

Anand³

et al. 2011

Blood

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One of the main functions of A Disintegrin and Metalloproteinase 10 (ADAM10) is to regulate the bioavailability of adhesion molecules and ligands to various cellularsignaling receptors. Constitutive activation of ADAM10 has been implicated in the pathogenesis of several types of solid tumors. In this study, we found that mantle cell lymphoma (MCL) cell lines and all 12 patient samples examined expressed the active/mature form of ADAM10. In contrast, PBMCs from healthy donors (n ‫؍‬ 5) were negative. Using immunohistochemistry, ADAM10 was readily detectable in 20 of 23 (87%) MCL tumors, but absent in 5 reactive tonsils. Knockdown of ADAM10 using short interfering RNA (siRNA) in MCL cells significantly induced growth inhibition and cell-cycle arrest, and these changes were correlated with down-regulation of cyclin D1, up-regulation of p21 waf1 , and significant reductions in the TNF␣ production/transcriptional activity of NFBp65. The addition of recombinant ADAM10 to MCL cells led to the opposite biologic effects. Lastly, down-regulation of ADAM10 using siRNA enhanced the growth-suppressing effects mediated by the proteasome inhibitors MG132 and bortezomib. We conclude that constitutive activation of ADAM10 contributes to the growth of MCL and therefore inhibition of ADAM10 may be a useful strategy to enhance the response of MCL to other therapeutic agents. IntroductionA Disintegrin and Metalloproteinase 10 (ADAM10), a member of the ADAM family of metalloproteinases, was discovered in the protein extract of brain myelin membranes and subsequently found to be a homolog of the Drosophila kuzbanian gene. [1][2][3] ADAM10 is secreted as a precursor protein and consists of multiple functional domains, including a prodomain, catalytic domain, cysteine-rich domain, transmembranous domain, and cytoplasmic domain. 4 To become the active/mature form, the precursor ADAM10 protein needs to be cleaved by proprotein convertase 7 and furin, both of which remove the ADAM10 prodomain. 5 ADAM10 is biologically important, because ADAM10 knockout mice die on day 9 of embryogenesis due to multiple abnormalities in the nervous and cardiovascular systems. 6 The key biologic function of ADAM10 appears to be attributed to its enzymatic activity as a metalloproteinase. Specifically, ADAM10 is involved in the intramembrane proteolysis process, whereby it mediates ectodomain shedding of various membrane-bound receptors, adhesion molecules, growth factors, and cytokines. [7][8][9] For example, ADAM10 is involved in the regulation of the shedding of Notch, HER-2, CD44, IL-6 receptor, amyloid precursor protein, and cadherins. 10 Directly relevant to our study, ADAM10 was recently found to be one of the enzymes responsible for cleaving TNF␣ and releasing its active form. [11][12][13] Furthermore, it has been reported that ADAM10 is important for the development of the marginal zone B cells. 14 By regulating the bioavailability of ligands to various cellular-signaling receptors, ADAM10 modulates the activation status of various cellularsignaling...

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Section: Adam10 Inhibition Enhanced the Growth-suppressing Effect Of supporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Constitutive activation of metalloproteinase ADAM10 in mantle cell lymphoma promotes cell growth and activates the TNFα/NFκB pathway

Armanious¹,

Gélébart²,

Anand³

et al. 2011

Blood

View full text Add to dashboard Cite

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“…The clustering outcomes made biological sense when compared with groups of eyes with morphologically recognizable stages of glaucoma. Clustering analyses have proven useful for identifying gene expression differences that distinguish various known types and stages of cancer (28,29). To our knowledge, clustering analysis has not been previously used to distinguish and order early states of a complex multifactorial disease (or any other disease) in samples that are morphologically similar to unaffected controls.…”

Section: Figurementioning

confidence: 99%

“…Clustering genes in microarray datasets according to their expression profiles is a powerful approach that has identified molecular signatures that predict cancer progression (28,29). Clustering methods group the most similar samples based on the expression profiles of many relevant genes.…”

Section: Introductionmentioning

confidence: 99%

Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma

Howell¹,

Macalinao²,

Sousa³

et al. 2011

J. Clin. Invest.

399

585

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Glaucoma is one of the most common neurodegenerative diseases. Despite this, the earliest stages of this complex disease are still unclear. This study was specifically designed to identify early stages of glaucoma in DBA/2J mice. To do this, we used genome-wide expression profiling of optic nerve head and retina and a series of computational methods. Eyes with no detectable glaucoma by conventional assays were grouped into molecularly defined stages of disease using unbiased hierarchical clustering. These stages represent a temporally ordered sequence of glaucoma states. We then determined networks and biological processes that were altered at these early stages. Early-stage expression changes included upregulation of both the complement cascade and the endothelin system, and so we tested the therapeutic value of separately inhibiting them. Mice with a mutation in complement component 1a (C1qa) were protected from glaucoma. Similarly, inhibition of the endothelin system with bosentan, an endothelin receptor antagonist, was strongly protective against glaucomatous damage. Since endothelin 2 is potently vasoconstrictive and was produced by microglia/macrophages, our data provide what we believe to be a novel link between these cell types and vascular dysfunction in glaucoma. Targeting early molecular events, such as complement and endothelin induction, may provide effective new treatments for human glaucoma.

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“…Hierarchical clustering is an unbiased computational method for grouping samples based on the similarity of their gene expression profiles. It is a powerful approach for characterizing stages of cancer and other diseases (26)(27)(28). Here, we used hierarchical clustering to analyze our gene expression data.…”

Section: Bone Marrow Transfer Is Not Required For Protectionmentioning

confidence: 99%

Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma

et al. 2012

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Immunoprofiles of 11 Biomarkers Using Tissue Microarrays Identify Prognostic Subgroups in Colorectal Cancer

Cited by 76 publications

References 32 publications

Constitutive activation of metalloproteinase ADAM10 in mantle cell lymphoma promotes cell growth and activates the TNFα/NFκB pathway

Constitutive activation of metalloproteinase ADAM10 in mantle cell lymphoma promotes cell growth and activates the TNFα/NFκB pathway

Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma

Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma

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