Inhibition of CX3CR1 reduces cell motility and viability in pancreatic adenocarcinoma epithelial cells

Stout, Matthew C.; Narayan, Shilpa; Pillet, Emily S.; Salvino, Joseph M.; Campbell, Paul M.

doi:10.1016/j.bbrc.2017.12.116

Cited by 15 publications

(7 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides, we further revealed that majority of infiltrated M2 macrophages strongly expressed CX3CR1, and both recombinant CX3CL1 and NP cells significantly induced M2 polarization of RAW264.7. While this effect was totally reversed by si-CX3CL1 or JMS-17-2, which has been frequently used as an inhibitor of CX3CR1 [ 17 ], indicating that CX3CL1/CX3CR1 axis was involved in the recruitment of M2 macrophages in the degenerated NP tissue.…”

Section: Discussionmentioning

confidence: 99%

Nucleus Pulposus Cells Induce M2 Polarization of RAW264.7 via CX3CL1/CX3CR1 Pathway and M2 Macrophages Promote Proliferation and Anabolism of Nucleus Pulposus Cells

Wan

Feng

et al. 2023

Stem Cells International

View full text Add to dashboard Cite

Background. The mechanisms underlying M2 macrophage polarization induced by nucleus pulposus (NP) cells are unclear. The effects that M2-polarized macrophages have on NP cells are also controversial. Methods. Transcriptome sequencing was performed to detect the gene change profiles between NP cells from ruptured intervertebral disc (IVD) and normal IVD. The main difference on biological activities between the two cell groups were analyzed by GO analysis and KEGG analysis. Virus transduction, flow cytometry, immunofluorescence, RT-PCR, western blot, CCK-8, TUNEL staining, and AO/EB staining were performed to explore the interactions between NP cells and RAW264.7 macrophages. Statistics were performed using SPSS26. Results. 801 upregulated and 276 downregulated genes were identified in NP cells from ruptured IVD in mouse models. According to GO and KEGG analysis, we found that the differentially expressed genes (DEG) were dominantly enriched in inflammatory response, extracellular matrix degradation, blood vessel morphogenesis, immune effector process, ossification, chemokine signaling pathway, macrophage activation, etc. CX3CL1 was one of the top 20% DEG, and we confirmed that both NP tissue and cells expressed remarkably higher level of CX3CL1 in mouse models ( p < 0.001 ∗ ). Besides, we further revealed that both the recombinant CX3CL1 and NP cells remarkably induced M2 polarization of RAW264.7 ( p < 0.001 ∗ ), respectively, while this effect was significantly reversed by si-CX3CL1 or JMS-17-2 ( p < 0.001 ∗ ). Furthermore, we found that M2 macrophages significantly decreased the apoptosis rate ( p < 0.001 ∗ ) and the catabolic gene levels ( p < 0.001 ∗ ) of NP cells, while increased the viability, proliferation as well as the anabolic gene levels of NP cells ( p < 0.01 ∗ ). Conclusions. Via regulating CX3CL1/CX3CR1 pathway, NP cells can induce the M2 macrophage polarization. M2 polarized macrophages can further promote NP cell viability, proliferation, and anabolism, while inhibit NP cell apoptosis and catabolism.

show abstract

Section: Discussionmentioning

confidence: 99%

Nucleus Pulposus Cells Induce M2 Polarization of RAW264.7 via CX3CL1/CX3CR1 Pathway and M2 Macrophages Promote Proliferation and Anabolism of Nucleus Pulposus Cells

Wan

Feng

et al. 2023

Stem Cells International

View full text Add to dashboard Cite

show abstract

“…To date, only a few anti-FKN drugs have been identified in the research market, including E6011 and JMS-17-2. The use of E6011 has been focused on assessing its effects on inflammatory conditions such as rheumatoid arthritis (RA) and Crohn's disease [89][90][91][92][93][94], whilst JMS-17-2 was particularly emphasised for its effects as an anti-cancer medication [100,101]. Tanaka et al had used a humanised monoclonal antibody called E6011 as its anti-FKN pharmacological therapy [102].…”

Section: Alternative Drugs To Target Fractalkine Signallingmentioning

confidence: 99%

Fractalkine Signalling (CX3CL1/CX3CR1 Axis) as an Emerging Target in Coronary Artery Disease

Loh,

Ekinci,

Spray

et al. 2023

JCM

View full text Add to dashboard Cite

Acute myocardial infarction (MI) is the most common and dramatic complication of atherosclerosis, which, despite successful reperfusion therapy, can lead to incident heart failure (HF). HF occurs when the healing process is impaired due to adverse left ventricular remodelling, and can be the result of so-called ischaemia/reperfusion injury (IRI), visualised by the development of intramyocardial haemorrhage (IMH) or microvascular obstruction (MVO) in cardiac MRI. Thus far, translation of novel pharmacological strategies from preclinical studies to target either IRI or HF post MI have been largely unsuccessful. Anti-inflammatory therapies also carry the risk of affecting the immune system. Fractalkine (FKN, CX3CL1) is a unique chemokine, present as a transmembrane protein on the endothelium, or following cleavage as a soluble ligand, attracting leukocyte subsets expressing the corresponding receptor CX3CR1. We have shown previously that the fractalkine receptor CX3CR1 is associated with MVO in patients undergoing primary PCI. Moreover, inhibition of CX3CR1 with an allosteric small molecule antagonist (KAND567) in the rat MI model reduces acute infarct size, inflammation, and IMH. Here we review the cellular biology of fractalkine and its receptor, along with ongoing studies that introduce CX3CR1 as a future target in coronary artery disease, specifically in patients with myocardial infarction.

show abstract

“…The CX3CL1-CX3CR1 axis has a direct action on molecules that facilitate invasion and metastasis, such as extracellular matrix metalloproteinases (MMPs), enzymes that have a central role on tissue remodeling. In studies carried out in the human cell line A549, it was found that knocking down CX3CL1 reduced MMP-2 and MMP-9 expression [97], and studies on pancreatic adenocarcinoma cells showed that the pharmacological inhibition of CX3CR1 with the selective antagonist JMS-17-2, decreased their motility and metastasis on a murine model of carcinogenesis [98,99]. It is important to evaluate in future research whether differential fragments of CX3CL1 are generated in the tumor microenvironment due to changes in expression patterns of metalloproteases in tissues undergoing remodeling.…”

Section: Cx3cl1-cx3cr1 In Cancermentioning

confidence: 99%

Regulation and biological functions of the CX3CL1-CX3CR1 axis and its relevance in solid cancer: A mini-review

Rivas-Fuentes¹,

Salgado-Aguayo²,

Arratia-Quijada³

et al. 2021

J. Cancer

View full text Add to dashboard Cite

CX3CL1 is a transmembrane protein from which a soluble form can be generated by proteolytic shedding. Membranal and soluble forms of CX3CL1 exhibit different functions, although both bind to the CX3CR1 chemokine receptor. The CX3CL1-CX3CR1 axis mediates the adhesion of leukocytes and is also involved in cell survival and recruitment of immune cell subpopulations. The function of CX3CL1 is finely tuned by cytokines and transcription factors regulating its expression and post-translational modifications. On homeostasis, the CX3CL1-CX3CR1 axis participates in the removal of damaged neurons and neurogenesis, and it is also involved on several pathological contexts. The CX3CL1-CX3CR1 axis induces several cellular responses relevant to cancer such as proliferation, migration, invasion and apoptosis resistance. In this review, we address biological aspects of this molecular axis with important therapeutic potential, emphasizing its role in cancer, one of the most prevalent chronic diseases which significantly affect the quality of life and life expectancy of patients.

show abstract

Inhibition of CX3CR1 reduces cell motility and viability in pancreatic adenocarcinoma epithelial cells

Cited by 15 publications

References 39 publications

Nucleus Pulposus Cells Induce M2 Polarization of RAW264.7 via CX3CL1/CX3CR1 Pathway and M2 Macrophages Promote Proliferation and Anabolism of Nucleus Pulposus Cells

Nucleus Pulposus Cells Induce M2 Polarization of RAW264.7 via CX3CL1/CX3CR1 Pathway and M2 Macrophages Promote Proliferation and Anabolism of Nucleus Pulposus Cells

Fractalkine Signalling (CX3CL1/CX3CR1 Axis) as an Emerging Target in Coronary Artery Disease

Regulation and biological functions of the CX3CL1-CX3CR1 axis and its relevance in solid cancer: A mini-review

Contact Info

Product

Resources

About