Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

Vallo, Stefan; Rutz, Jochen; Kautsch, Miriam; Winkelmann, Ria; Michaelis, Martin; Wezel, Felix; Bartsch, Georg; Haferkamp, Axel; Rothweiler, Florian; Blaheta, Roman A.; Cinatl, Jindrich

doi:10.3892/ol.2017.6883

Cited by 8 publications

(8 citation statements)

References 26 publications

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“…Additionally, we confirmed impact of selected CAMs on single B-cell adhesion in optical tweezers by using of function-blocking antibodies to β integrins and cadherin-2 on representative cell lines and primary B-cells. We observed that the formation of adhesion between B-cell and MSC prolonged significantly when β1 integrin and cadherin-2 were blocked with appropriate antibody what is in line with literature [ 61 , 62 , 63 ].…”

Section: Discussionsupporting

confidence: 90%

Physiological Hypoxia (Physioxia) Impairs the Early Adhesion of Single Lymphoma Cell to Marrow Stromal Cell and Extracellular Matrix. Optical Tweezers Study

Duś‐Szachniewicz

Drobczyński

Ziółkowski

et al. 2018

IJMS

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Adhesion is critical for the maintenance of cellular structures as well as intercellular communication, and its dysfunction occurs prevalently during cancer progression. Recently, a growing number of studies indicated the ability of oxygen to regulate adhesion molecules expression, however, the influence of physiological hypoxia (physioxia) on cell adhesion remains elusive. Thus, here we aimed: (i) to develop an optical tweezers based assay to precisely evaluate single diffuse large B-cell lymphoma (DLBCL) cell adhesion to neighbor cells (mesenchymal stromal cells) and extracellular matrix (Matrigel) under normoxia and physioxia; and, (ii) to explore the role of integrins in adhesion of single lymphoma cell. We identified the pronouncedly reduced adhesive properties of lymphoma cell lines and primary lymphocytes B under physioxia to both stromal cells and Matrigel. Corresponding effects were shown in bulk adhesion assays. Then we emphasized that impaired β1, β2 integrins, and cadherin-2 expression, studied by confocal microscopy, account for reduction in lymphocyte adhesion in physioxia. Additionally, the blockade studies conducted with anti-integrin antibodies have revealed the critical role of integrins in lymphoma adhesion. To summarize, the presented approach allows for precise confirmation of the changes in single cell adhesion properties provoked by physiological hypoxia. Thus, our findings reveal an unprecedented role of using physiologically relevant oxygen conditioning and single cell adhesion approaches when investigating tumor adhesion in vitro.

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Section: Discussionsupporting

confidence: 90%

Physiological Hypoxia (Physioxia) Impairs the Early Adhesion of Single Lymphoma Cell to Marrow Stromal Cell and Extracellular Matrix. Optical Tweezers Study

Duś‐Szachniewicz

Drobczyński

Ziółkowski

et al. 2018

IJMS

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“…The integrin β subunit has been characterized as a therapeutic target due to its abundance in high-grade bladder cancer cells and correlation with mitomycin resistance (Zhang et al, 2012). The application of integrin β1 antibody was shown to attenuate adhesive and invasive behaviors in drug-resistant urothelial cancer cell lines (Vallo et al, 2017). In addition, integrin signal transduction was found to recruit FAK and paxillin, which are required for intracellular integrin signal transduction (López-Colomé et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Pharmaceutical Evaluation of Honokiol and Magnolol on Apoptosis and Migration Inhibition in Human Bladder Cancer Cells

et al. 2020

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Among herbal medicines, magnolia bark extract, particularly its components honokiol (Hono) and magnolol (Mag), has been widely documented to have antineoplastic properties. The present study aimed to evaluate the synergism of Hono and Mag in bladder cancer therapy both in vitro and in vivo. Treatment with Mag alone at concentrations up to 80 μM failed to have an antiproliferative effect. In contrast, the combination of Hono and Mag at 40 μM decreased viability, caused cell cycle arrest and enhanced the proportion of Annexin V/7AAD-positive cells. Moreover, Mag with Hono at 40 μM induced caspase 3-dependent apoptosis and autophagy. Neither Hono nor Mag alone had an anti-migratory effect on bladder cancer cells. In contrast, Hono and Mag at 20 μM inhibited the motility of TSGH8301 and T24 cells in wound-healing and Transwell assays. The above phenomena were further confirmed by decreased phosphorylated focal adhesion kinase (p-FAK), p-paxillin, integrin β1, and integrin β3 protein levels. In a nude mouse xenograft model, Mag/Hono administration preferentially retarded T24 tumor progression, which was consistent with the results of cellular experiments. Current findings suggest Hono and Mag treatment as a potential anticancer therapy for both low-and highgrade urothelial carcinoma.

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“…This also reveals the concordance of our previous findings where we identified the activation of integrin signaling in the non-type bladder carcinoma. Targeting integrins have shown to decrease angiogenesis, tumor growth and metastasis in other cancers including bladder carcinoma [36,37,38]. FAK activation has also been reported to regulate bladder cancer invasion and migration which also makes it a favorable therapeutic target for bladder carcinoma [39].…”

Section: Discussionmentioning

confidence: 99%

N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma

Deb

Patel

Sathe

et al. 2019

JCM

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Treatment of advanced and metastatic bladder carcinoma is often ineffective and displays variable clinical outcomes. Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies. The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability. Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology. Here, we report the comparative analysis of N-linked glycosylation across bladder cancer subtypes. To analyze the glycosite-containing peptides, we carried out LC-MS/MS-based quantitative proteomic and glycoproteomic profiling. We identified 1299 unique N-linked glycopeptides corresponding to 460 proteins. Additionally, we identified 118 unique N-linked glycopeptides corresponding to 84 proteins to be differentially glycosylated only in non-type subtypes as compared to luminal/basal subtypes. Most of the altered glycoproteins were also observed with changes in their global protein expression levels. However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes. Importantly, the extracellular matrix organization pathway was dysregulated in the non-type subtype of bladder carcinoma. N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype. These aberrant protein glycosylation would provide additional avenues to employ glycan-based therapies and may lead to the identification of novel therapeutic targets.

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Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

Cited by 8 publications

References 26 publications

Physiological Hypoxia (Physioxia) Impairs the Early Adhesion of Single Lymphoma Cell to Marrow Stromal Cell and Extracellular Matrix. Optical Tweezers Study

Physiological Hypoxia (Physioxia) Impairs the Early Adhesion of Single Lymphoma Cell to Marrow Stromal Cell and Extracellular Matrix. Optical Tweezers Study

Pharmaceutical Evaluation of Honokiol and Magnolol on Apoptosis and Migration Inhibition in Human Bladder Cancer Cells

N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma

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