Only in Titles

           Search results for: Mouse Anti Human CD29 CD29   

paperclip

#29281661   // Save this To Up

The anti-tumorigenic activity of A2M-A lesson from the naked mole-rat.

Cancer resistance is a major cause for longevity of the naked mole-rat. Recent liver transcriptome analysis in this animal compared to wild-derived mice revealed higher expression of alpha2-macroglobulin (A2M) and cell adhesion molecules, which contribute to the naked mole-rat's cancer resistance. Notably, A2M is known to dramatically decrease with age in humans. We hypothesize that this might facilitate tumour development. Here we found that A2M modulates tumour cell adhesion, migration and growth by inhibition of tumour promoting signalling pathways, e.g. PI3K / AKT, SMAD and up-regulated PTEN via down-regulation of miR-21, in vitro and in tumour xenografts. A2M increases the expression of CD29 and CD44 but did not evoke EMT. Transcriptome analysis of A2M-treated tumour cells, xenografts and mouse liver demonstrated a multifaceted regulation of tumour promoting signalling pathways indicating a less tumorigenic environment mediated by A2M. By virtue of these multiple actions the naturally occurring A2M has strong potential as a novel therapeutic agent.

2160 related Products with: The anti-tumorigenic activity of A2M-A lesson from the naked mole-rat.

Rat Anti-CCT theta Antibo Normal rat multiple organ Normal rat multiple organ Normal rat multiple organ Rabbit anti PKC theta (Ab Rabbit anti PKC theta (Ab Rabbit anti PKC theta (Ab Rabbit Anti-Theophylline Sheep Anti-Theophylline 3 FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu

Related Pathways

  •  
  • No related Items
paperclip

#29117236   // Save this To Up

Effects of CD49d-targeted antisense-oligonucleotide on α4 integrin expression and function of acute lymphoblastic leukemia cells: Results of in vitro and in vivo studies.

We recently demonstrated the effectiveness of blocking CD49d with anti-functional antibodies or small molecule inhibitors as a rational targeted approach to the treatment of acute leukemia in combination with chemotherapy. Antisense oligonucleotide promises to be no less specific than antibodies and inhibitors, but more interesting for pharmacokinetics and pharmacodynamics. We addressed this using the published CD49d antisense drug ATL1102. In vitro, we incubated/nucleofected the ALL cell line Kasumi-2 with ATL1102. In vivo, immunodeficient hosts were engrafted with primary ALL cells and treated with ATL1102. Changes in expression of CD49d mRNA and CD49d protein, and of cooperating gene products, including ß1 integrin and CXCR4, as well as survival in the mouse experiments were quantified. We observed dose-dependent down-regulation of CD49d mRNA and protein levels and its partner integrin ß1 cell surface protein level and, up-regulation of CXCR4 surface expression. The suppression was more pronounced after nucleofection than after incubation, where down-regulation was significant only at the higher doses. In vivo effects of ATL1102 were not sufficient to translate into "clinical" benefit in the leukemia model. In summary, antisense oligonucleotides are successful tools for specifically modulating gene expression but sufficient delivery to down-regulate CD49d in vivo may be difficult to achieve.

2919 related Products with: Effects of CD49d-targeted antisense-oligonucleotide on α4 integrin expression and function of acute lymphoblastic leukemia cells: Results of in vitro and in vivo studies.

LPAM-1(Integrin α4, CD49 Human integrin aVb3, affi Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph

Related Pathways

paperclip

#29109269   // Save this To Up

Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8.

Human regulatory T cells (Tregs) suppress other T cells by converting the latent, inactive form of TGF-β1 into active TGF-β1. In Tregs, TGF-β1 activation requires GARP, a transmembrane protein that binds and presents latent TGF-β1 on the surface of Tregs stimulated through their T cell receptor. However, GARP is not sufficient because transduction of GARP in non-Treg T cells does not induce active TGF-β1 production. RGD-binding integrins were shown to activate TGF-β1 in several non-T cell types. Here we show that αVβ8 dimers are present on stimulated human Tregs but not in other T cells, and that antibodies against αV or β8 subunits block TGF-β1 activation in vitro. We also show that αV and β8 interact with GARP/latent TGF-β1 complexes in human Tregs. Finally, a blocking antibody against β8 inhibited immunosuppression by human Tregs in a model of xenogeneic graft-vs.-host disease induced by the transfer of human T cells in immunodeficient mice. These results show that TGF-β1 activation on the surface of human Tregs implies an interaction between the integrin αVβ8 and GARP/latent TGF-β1 complexes. Immunosuppression by human Tregs can be inhibited by antibodies against GARP or against the integrin β8 subunit. Such antibodies may prove beneficial against cancer or chronic infections.

2002 related Products with: Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8.

Goat Anti-Human, Mouse In Mouse anti human Integrin Mouse anti human Integrin Mouse anti human Integrin Mouse anti human Integrin Mouse anti human Integrin Mouse anti human Integrin Mouse anti human Integrin Mouse anti human Integrin Goat Anti-Human Synaptota Goat Anti-Human STK39 SPA Goat Anti-Human SPHK1, (i

Related Pathways

paperclip

#28877991   // Save this To Up

Activated Protein C Attenuates Severe Inflammation by Targeting VLA-3high Neutrophil Subpopulation in Mice.

The host injury involved in multiorgan system failure during severe inflammation is mediated, in part, by massive infiltration and sequestration of hyperactive neutrophils in the visceral organ. A recombinant form of human activated protein C (rhAPC) has shown cytoprotective and anti-inflammatory functions in some clinical and animal studies, but the direct mechanism is not fully understood. Recently, we reported that, during endotoxemia and severe polymicrobial peritonitis, integrin VLA-3 (CD49c/CD29) is specifically upregulated on hyperinflammatory neutrophils and that targeting the VLA-3high neutrophil subpopulation improved survival in mice. In this article, we report that rhAPC binds to human neutrophils via integrin VLA-3 (CD49c/CD29) with a higher affinity compared with other Arg-Gly-Asp binding integrins. Similarly, there is preferential binding of activated protein C (PC) to Gr1highCD11bhighVLA-3high cells isolated from the bone marrow of septic mice. Furthermore, specific binding of rhAPC to human neutrophils via VLA-3 was inhibited by an antagonistic peptide (LXY2). In addition, genetically modified mutant activated PC, with a high affinity for VLA-3, shows significantly improved binding to neutrophils compared with wild-type activated PC and significantly reduced neutrophil infiltration into the lungs of septic mice. These data indicate that variants of activated PC have a stronger affinity for integrin VLA-3, which reveals novel therapeutic possibilities.

1680 related Products with: Activated Protein C Attenuates Severe Inflammation by Targeting VLA-3high Neutrophil Subpopulation in Mice.

Anti C Reactive Protein A Human Macrophage Inflamma Human Macrophage Inflamma Human Macrophage Inflamma Human Macrophage Inflamma Human Macrophage Inflamma Human Gro g Macrophage In Mouse Macrophage Inflamma Mouse Macrophage Inflamma Mouse Macrophage Inflamma Mouse Macrophage Inflamma Native Influenza HA (A Ca

Related Pathways

paperclip

#28771231   // Save this To Up

FGFR1 is critical for the anti-endothelial mesenchymal transition effect of N-acetyl-seryl-aspartyl-lysyl-proline via induction of the MAP4K4 pathway.

Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to organ fibrogenesis, and we have reported that the anti-EndMT effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is associated with restoring expression of diabetes-suppressed fibroblast growth factor receptor (FGFR), the key anti-EndMT molecule. FGFR1 is the key inhibitor of EndMT via the suppression of the transforming growth factor β (TGFβ) signaling pathway, and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) inhibits integrin β1, a key factor in activating TGFβ signaling and EndMT. Here, we showed that the close proximity between AcSDKP and FGFR1 was essential for the suppression of TGFβ/smad signaling and EndMT associated with MAP4K4 phosphorylation (P-MAP4K4) in endothelial cells. In cultured human dermal microvascular endothelial cells (HMVECs), the anti-EndMT and anti-TGFβ/smad effects of AcSDKP were lost following treatment with a neutralizing FGFR1 antibody (N-FGFR1) or transfection of FRS2 siRNA. The physical interaction between FGFR1 and P-MAP4K4 in HMVECs was confirmed by proximity ligation analysis and an immunoprecipitation assay. AcSDKP induced P-MAP4K4 in HMVECs, which was significantly inhibited by treatment with either N-FGFR1 or FRS2 siRNA. Furthermore, MAP4K4 knockdown using specific siRNAs induced smad3 phosphorylation and EndMT in HMVECs, which was not suppressed by AcSDKP. Streptozotocin-induced diabetic CD-1 mice exhibited suppression of both FGFR1 and P-MAP4K4 expression levels associated with the induction of TGFβ/smad3 signaling and EndMT in their hearts and kidneys; those were restored by AcSDKP treatment. These data demonstrate that the AcSDKP-FGFR1-MAP4K4 axis has an important role in combating EndMT-associated fibrotic disorders.

1823 related Products with: FGFR1 is critical for the anti-endothelial mesenchymal transition effect of N-acetyl-seryl-aspartyl-lysyl-proline via induction of the MAP4K4 pathway.

MOUSE ANTI BOVINE ROTAVIR MOUSE ANTI BORRELIA BURGD RABBIT ANTI GSK3 BETA (pS Rabbit anti PKC theta (Ab Rabbit anti PKC theta (Ab Rabbit anti PKC theta (Ab Rabbit Anti-bFGFR FGFR1 P Rabbit Anti-bFGFR FGFR1 P Rabbit Anti-bFGFR FGFR1 P Rabbit Anti-bFGFR FGFR1 P Rabbit Anti-bFGFR FGFR1 P Rabbit Anti-bFGFR FGFR1 P

Related Pathways

paperclip

#28692661   // Save this To Up

The extracellular matrix and focal adhesion kinase signaling regulate cancer stem cell function in pancreatic ductal adenocarcinoma.

Cancer stem cells (CSCs) play an important role in the clonogenic growth and metastasis of pancreatic ductal adenocarcinoma (PDAC). A hallmark of PDAC is the desmoplastic reaction, but the impact of the tumor microenvironment (TME) on CSCs is unknown. In order to better understand the mechanisms, we examined the impact of extracellular matrix (ECM) proteins on PDAC CSCs. We quantified the effect of ECM proteins, β1-integrin, and focal adhesion kinase (FAK) on clonogenic PDAC growth and migration in vitro and tumor initiation, growth, and metastasis in vivo in nude mice using shRNA and overexpression constructs as well as small molecule FAK inhibitors. Type I collagen increased PDAC tumor initiating potential, self-renewal, and the frequency of CSCs through the activation of FAK. FAK overexpression increased tumor initiation, whereas a dominant negative FAK mutant or FAK kinase inhibitors reduced clonogenic PDAC growth in vitro and in vivo. Moreover, the FAK inhibitor VS-4718 extended the anti-tumor response to gemcitabine and nab-paclitaxel in patient-derived PDAC xenografts, and the loss of FAK expression limited metastatic dissemination of orthotopic xenografts. Type I collagen enhances PDAC CSCs, and both kinase-dependent and independent activities of FAK impact PDAC tumor initiation, self-renewal, and metastasis. The anti-tumor impact of FAK inhibitors in combination with standard chemotherapy support the clinical testing of this combination.

1670 related Products with: The extracellular matrix and focal adhesion kinase signaling regulate cancer stem cell function in pancreatic ductal adenocarcinoma.

Macrophage Colony Stimula Macrophage Colony Stimula Glucagon ELISA KIT, Rat G T-Cell Receptor Signaling High density (188 cases 2 High density (188 cases 2 Human breast invasive duc p130Cas-associated protei DiscoveryPak™ Stem Cell PathwayReady™ MAP Kinas Lung non small cell cance Oral squamous cell cancer

Related Pathways

paperclip

#28684854   // Save this To Up

Prospectively isolated mesenchymal stem/stromal cells are enriched in the CD73+ population and exhibit efficacy after transplantation.

Mesenchymal stem/stromal cells (MSCs), which reside in the bone marrow (BM) and various other tissues, can self-renew and differentiate into mesenchymal lineages. Many groups have harvested rat MSCs (rMSCs) from rat BM (rBM) by using a flush-out procedure and have evaluated surface marker expression after long-term culture. However, MSCs gradually differentiate during expansion and exhibit altered proliferation rates, morphological features and functions in vitro. Variations in MSC isolation methods may alter the effectiveness of therapeutic applications. Here, on the basis of CD29 (Itgb1) and CD54 (Icam1) expression, we prospectively isolated a population with a high colony-forming ability and multi-lineage potential from the rBM, and we demonstrated that most of these cells expressed CD73. Successful engraftment of rMSCs was achieved by using a fluorescence-conjugated anti-CD73 antibody. In humans and mice, MSCs were also purified by CD73, thus suggesting that CD73 may serve as a universal marker for prospective isolation of MSCs. Our results may facilitate investigations of MSC properties and function.

1177 related Products with: Prospectively isolated mesenchymal stem/stromal cells are enriched in the CD73+ population and exhibit efficacy after transplantation.

Macrophage Colony Stimula Macrophage Colony Stimula Rat Mesenchymal Stem Cell Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon anti HSV (II) gB IgG1 (mo anti HCMV IE pp65 IgG1 (m anti HCMV gB IgG1 (monocl Goat Anti-Human, Mouse AR GLP 1 ELISA Kit, Rat Gluc

Related Pathways

paperclip

#28667248   // Save this To Up

Suppression of αvβ6 Integrin Expression by Polymicrobial Oral Biofilms in Gingival Epithelial Cells.

Periodontal diseases manifest by the formation of deep pockets between the gingiva and teeth where multispecies bacterial biofilms flourish, causing inflammation and bone loss. Epithelial cell receptor αvβ6 integrin that regulates inflammation by activating the anti-inflammatory cytokine transforming growth factor-β1, is highly expressed in healthy junctional epithelium that connects the gingiva to the tooth enamel. However, its expression is attenuated in human periodontal disease. Moreover, Itgb6 -/- mice display increased periodontal inflammation compared to wild-type mice. We hypothesized that bacterial biofilms present in the periodontal pockets suppress αvβ6 integrin levels in periodontal disease and that this change aggravates inflammation. To this end, we generated three-week-old multi-species oral biofilms in vitro and treated cultured gingival epithelial cells (GECs) with their extracts. The biofilm extracts caused suppression of β6 integrin expression and upregulation of pro-inflammatory cytokines, including interleukin-1β and -6. Furthermore, GECs with β6 integrin siRNA knockdown showed increased interleukin-1β expression, indicating that αvβ6 integrin-deficiency is associated with pro-inflammatory cytokine responsiveness. FSL-1, a synthetic bacterial lipopeptide, also suppressed β6 integrin expression in GECs. Therefore, biofilm components, including lipopeptides, may downregulate αvβ6 integrin expression in the pocket epithelium and thus promote epithelial cell-driven pro-inflammatory response in periodontal disease.

2480 related Products with: Suppression of αvβ6 Integrin Expression by Polymicrobial Oral Biofilms in Gingival Epithelial Cells.

anti HSV (II) gB IgG1 (mo anti HCMV IE pp65 IgG1 (m anti HCMV gB IgG1 (monocl DNA (cytosine 5) methyltr Integrin â3 (Phospho Tyr Integrin â3 (Phospho Tyr Macrophage Colony Stimula Macrophage Colony Stimula Integrin â3 (Ab 773) Ant Integrin â3 (Ab 785) Ant Integrin β1 (CD29) Antib LPAM-1(Integrin α4, CD49

Related Pathways

paperclip

#28552668   // Save this To Up

β1-Integrin Accumulates in Cystic Fibrosis Luminal Airway Epithelial Membranes and Decreases Sphingosine, Promoting Bacterial Infections.

Chronic pulmonary colonization with bacterial pathogens, particularly Pseudomonas aeruginosa, is the primary cause of morbidity and mortality in patients with cystic fibrosis (CF). We observed that β1-integrins accumulate on the luminal membrane of upper-airway epithelial cells from mice and humans with CF. β1-integrin accumulation is due to increased ceramide and the formation of ceramide platforms that trap β1-integrins on the luminal pole of bronchial epithelial cells. β1-integrins downregulate acid ceramidase expression, resulting in further accumulation of ceramide and consequent reduction of surface sphingosine, a lipid that kills bacteria. Interrupting this vicious cycle by triggering surface β1-integrin internalization via anti-β1-integrin antibodies or the RGD peptide ligand-or by genetic or pharmacological correction of ceramide levels-normalizes β1-integrin distribution and sphingosine levels in CF epithelial cells and prevents P. aeruginosa infection in CF mice. These findings suggest a therapeutic avenue to ameliorate CF-associated bacterial infections.

2336 related Products with: β1-Integrin Accumulates in Cystic Fibrosis Luminal Airway Epithelial Membranes and Decreases Sphingosine, Promoting Bacterial Infections.

Integrin β1 (CD29) Antib Integrin â3 (Phospho Tyr Integrin â3 (Phospho Tyr Integrin â3 (Ab 773) Ant Integrin â3 (Ab 785) Ant LPAM-1(Integrin α4, CD49 Integrin alphaX antibody CD41 Integrin alpha 2b an Integrin alpha6 antibody Human integrin aVb3, affi Angiogenesis (Human) Anti Angiogenesis (Human) Anti

Related Pathways

paperclip

#28448494   // Save this To Up

Integrin β1 activation induces an anti-melanoma host response.

TGF-β is a cytokine thought to function as a tumor promoter in advanced malignancies. In this setting, TGF-β increases cancer cell proliferation, survival, and migration, and orchestrates complex, pro-tumorigenic changes in the tumor microenvironment. Here, we find that in melanoma, integrin β1-mediated TGF-β activation may also produce tumor suppression via an altered host response. In the A375 human melanoma cell nu/nu xenograft model, we demonstrate that cell surface integrin β1-activation increases TGF-β activity, resulting in stromal activation, neo-angiogenesis and, unexpectedly for this nude mouse model, increase in the number of intra-tumoral CD8+ T lymphocytes within the tumor microenvironment. This is associated with attenuation of tumor growth and long-term survival benefit. Correspondingly, in human melanomas, TGF-β1 correlates with integrin β1/TGF-β1 activation and the expression of markers for vasculature and stromal activation. Surprisingly, this integrin β1/TGF-β1 transcriptional footprint also correlates with the expression of markers for tumor-infiltrating lymphocytes, multiple immune checkpoints and regulatory pathways, and, importantly, better long-term survival of patients. These correlations are unique to melanoma, in that we do not observe similar associations between β1 integrin/TGF-β1 activation and better long-term survival in other human tumor types. These results suggest that activation of TGF-β1 in melanoma may be associated with the generation of an anti-tumor host response that warrants further study.

2225 related Products with: Integrin β1 activation induces an anti-melanoma host response.

MOUSE ANTI BOVINE ROTAVIR Mouse anti Human IgA anti Mouse anti IgA1 antibody, Mouse anti Human IgE anti Mouse anti Human IgE anti Mouse anti Human IgE anti Mouse anti Human IgE anti Mouse anti Canine IgE ant Mouse anti Canine IgE ant Mouse anti Canine IgE ant Mouse anti Canine IgE ant Mouse anti Human IgG anti

Related Pathways