Decoy Receptor 3 Expression in AsPC-1 Human Pancreatic Adenocarcinoma Cells via the Phosphatidylinositol 3-Kinase-, Akt-, and NF-κB-Dependent Pathway

Chen, Pei-Hsuan; Yang, Chung-May

doi:10.4049/jimmunol.181.12.8441

Cited by 34 publications

(18 citation statements)

References 45 publications

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“…In addition, our unpublished observations (M. (47). Therefore, DcR3 might be a negative-feedback regulator of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Decoy Receptor 3 Suppresses TLR2-Mediated B Cell Activation by Targeting NF-κB

Huang¹,

Kang²,

Chen³

et al. 2012

The Journal of Immunology

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Decoy receptor 3 (DcR3) is a soluble protein in the TNFR superfamily. Its known ligands include Fas ligand, homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes, TNF-like molecule 1A, and heparan sulfate proteoglycans. DcR3 has been reported to modulate the functions of T cells, dendritic cells, and macrophages; however, its role in regulating B cell activation is largely unknown. In this study, we found that the DcR3.Fc fusion protein bound to human and mouse B cells and suppressed the activation of B cells. DcR3.Fc attenuated Staphylococcus aureus, IgM-, Pam3CSK4-, and LPS-mediated B cell proliferation but did not affect cytokine-induced B cell growth. In the presence of these mitogens, DcR3.Fc did not induce B cell apoptosis, suggesting that DcR3 may inhibit the signal(s) important for B cell activation. Because the combination of Fas.Fc, LT-βR.Fc (homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes receptor), and DR3.Fc (TNF-like molecule 1A receptor) did not suppress B cell proliferation and because the biological effect of DcR3.Fc on B cells was not blocked by heparin, we hypothesize that a novel ligand(s) of DcR3 mediates its inhibitory activity on B cells. Moreover, we found that TLR2-stimulated NF-κB p65 activation and NF-κB–driven luciferase activity were attenuated by DcR3.Fc. The TLR2-induced cytokine production by B cells was consistently reduced by DcR3. These results imply that DcR3 may regulate B cell activation by suppressing the activation of NF-κB.

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“…In addition, our unpublished observations (M. (47). Therefore, DcR3 might be a negative-feedback regulator of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Decoy Receptor 3 Suppresses TLR2-Mediated B Cell Activation by Targeting NF-κB

Huang¹,

Kang²,

Chen³

et al. 2012

The Journal of Immunology

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“…Knockdown of DcR3 in vivo (in mice xenografts) inhibited pancreatic cancer tumor growth, demonstrating the importance of this protein in cancer progression and suggesting that DcR3 is a potential therapeutic target [27] . Different treatments have been shown to reduce high concentrations of DcR3 in pancreatic adenocarcinoma cells (a tyrosine kinase and a PI3K inhibitor, an NF-κB inhibitor, and an insulin-like growth factor 1 inhibitor) [28] , indicating potential new treatment options also in SI-NETs. The specificity and sensitivity of DcR3 as a prognostic biomarker were good according to the ROC curve analysis, and further analyses in a larger cohort should be performed to confirm its clinical potential as a biomarker for bulky disease and prognosis.…”

Section: Discussionmentioning

confidence: 99%

DcR3, TFF3, and Midkine Are Novel Serum Biomarkers in Small Intestinal Neuroendocrine Tumors

Edfeldt¹,

Daskalakis²,

Bäcklin³

et al. 2016

Neuroendocrinology

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Small intestinal neuroendocrine tumors (SI-NETs) are amine- and peptide-producing neoplasms. Most patients display metastases at the time of diagnosis; they have an unpredictable individual disease course and the tumors are often therapy resistant. Chromogranin A and 5-hydroxyindoleacetic acid are the biomarkers clinically used most often today, but there is a great need for novel diagnostic and prognostic biomarkers and new therapeutic targets. Sixty-nine biomarkers were screened in serum from 23 SI-NET patients and 23 healthy controls using the multiplex proximity ligation assay (PLA). A refined method, the proximity extension assay (PEA), was used to analyze 76 additional biomarkers. Statistical testing and multivariate classification were performed. Immunohistochemistry and ELISA were performed in an extended cohort. Using PLA, 19 biomarkers showed a significant difference in serum concentrations between patients and controls, and PEA revealed a difference in the concentrations of 17 proteins. Multivariate classification analysis revealed decoy receptor 3 (DcR3), trefoil factor 3 (TFF3), and midkine to be good biomarkers for the disease, which was confirmed by ELISA analysis. All 3 biomarkers were expressed in tumor tissue. DcR3 concentrations were elevated in patients with stage IV disease. High concentrations of DcR3 and TFF3 were correlated to poor survival. DcR3, TFF3, and midkine exhibited elevated serum concentrations in SI-NET patients compared to healthy controls, and DcR3 and TFF3 were associated with poor survival. DcR3 seems to be a marker for liver metastases, while TFF3 and midkine may be new diagnostic biomarkers for SI-NETs.

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“…Increased expression of the PI3K catalytic subunit genes and an increase in Akt activity has been observed in pancreatic cancer cells [13]. Interestingly, which may lead to activation of Akt, was shown to be correlated with metastatic pancreatic cancer [11,14]. Furthermore, activation of Akt has been suggested to be associated with chemoresistance of aggressive pancreatic cancer [15,16].…”

Section: Introductionmentioning

confidence: 95%

Activation of the PI3K/Akt Pathway Mediates Bone Morphogenetic Protein 2-Induced Invasion of Pancreatic Cancer Cells Panc-1

Chen

Liao

et al. 2010

Pathol. Oncol. Res.

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Bone morphogenetic proteins (BMPs) signaling has an emerging role in pancreatic cancer. However, because of the multiple effects of different BMPs, no final conclusions have been made as to the role of BMPs in pancreatic cancer. In our studies, we have focused on bone morphogenetic protein 2(BMP-2) because it induces an epithelial to mesenchymal transition (EMT) and accelerates invasion in the human pancreatic cancer cell line Panc-1. It has been reported that the phosphatidylinositol 3-kinase (PI3K)/Akt pathway mediates invasion of gastric and colon cancer cells, which is unrevealed in pancreatic cancer cells. The objective of our study was to investigate whether BMP-2 mediated invasion might pass through the PI3K/Akt pathway. Our results show that expression of phosphorylation of Akt was increased by treatment with BMP-2, but not Noggin, a BMP-2 antagonist. Then pretreatment of Panc-1 cells with LY294002, an inhibitor of the PI3K/AKT pathway, significantly inhibited BMP-2-induced EMT and invasiveness. The data suggest that BMP-2 accelerates invasion of panc-1 cells via the PI3K/AKT pathway in panc-1 cells, which gives clues to searching new therapy targets in advanced pancreatic cancer.

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Decoy Receptor 3 Expression in AsPC-1 Human Pancreatic Adenocarcinoma Cells via the Phosphatidylinositol 3-Kinase-, Akt-, and NF-κB-Dependent Pathway

Cited by 34 publications

References 45 publications

Decoy Receptor 3 Suppresses TLR2-Mediated B Cell Activation by Targeting NF-κB

Decoy Receptor 3 Suppresses TLR2-Mediated B Cell Activation by Targeting NF-κB

DcR3, TFF3, and Midkine Are Novel Serum Biomarkers in Small Intestinal Neuroendocrine Tumors

Activation of the PI3K/Akt Pathway Mediates Bone Morphogenetic Protein 2-Induced Invasion of Pancreatic Cancer Cells Panc-1

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