Growth, metastasis, and expression of CCL2 and CCL5 by murine mammary carcinomas are dependent upon Myd88

Egunsola, Adetutu T.; Zawislak, Carolyn L.; Akuffo, Afua A.; Chalmers, Samantha A.; Ewer, Jason; Vail, Caroline; Lombardo, Jeffrey; Perez, Dana; Kurt, Robert A.

doi:10.1016/j.cellimm.2011.10.008

Cited by 24 publications

(32 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, MyD88 is required for nerve injury induced upregulation of CCL2, in DRG neurons (Fig. 6E,F), consistent with another report in which the release of CCL2 was dependent on MyD88 pathway in murine mammary carcinomas cells23. Previous studies showed that CCL2, upregulated in DRG neurons after nerve injury27, could increase Na v 1.8 activity and excitability of DRG neurons22, leading to an enhanced neuropathic pain state.…”

Section: Discussionsupporting

confidence: 90%

See 1 more Smart Citation

TLR signaling adaptor protein MyD88 in primary sensory neurons contributes to persistent inflammatory and neuropathic pain and neuroinflammation

Liu

Chen

et al. 2016

Sci Rep

100

View full text Add to dashboard Cite

Increasing evidence suggests that neuro-immune and neuro-glial interactions are critically involved in chronic pain sensitization. It is well studied how immune/glial mediators sensitize pain, but how sensory neurons control neuroinflammation remains unclear. We employed Myd88 conditional knockout (CKO) mice, in which Myd88 was deleted in sodium channel subunit Nav1.8-expressing primary sensory neurons, to examine the unique role of neuronal MyD88 in regulating acute and chronic pain, and possible underlying mechanisms. We found that baseline pain and the formalin induced acute inflammatory pain were intact in CKO mice. However, the late phase inflammatory pain following complete Freund’s adjuvant injection and the late phase neuropathic pain following chronic constriction injury (CCI), were reduced in CKO mice. CCI induced up-regulation of MyD88 and chemokine C-C motif ligand 2 expression in DRG neurons and macrophage infiltration into DRGs, and microglia activation in spinal dorsal horns in wild-type mice, but all these changes were compromised in CKO mice. Finally, the pain hypersensitivity induced by intraplantar IL-1β was reduced in CKO mice. Our findings suggest that MyD88 in primary sensory neurons plays an active role in regulating IL-1β signaling and neuroinflammation in the peripheral and the central nervous systems, and contributes to the maintenance of persistent pain.

show abstract

Section: Discussionsupporting

confidence: 90%

“…CCL2 was shown to increase Na v 1.8 activity and excitability of DRG neurons2122. Notably, CCL2 expression was found to be dependent on MyD88 in murine mammary carcinomas cells23. We postulated that primary sensory neurons recruit macrophages to DRGs through chemokine release.…”

Section: Resultsmentioning

confidence: 89%

TLR signaling adaptor protein MyD88 in primary sensory neurons contributes to persistent inflammatory and neuropathic pain and neuroinflammation

Liu

Chen

et al. 2016

Sci Rep

100

View full text Add to dashboard Cite

show abstract

“…In addition, it has also been revealed that tumor protein p53 binds to CCL2, consequently significantly downregulating CCL2 promoter activity, and thus suppressing CCL2-induced subcutaneous tumor xenografts (49). CCL2 may be regulated by myeloid differentiation primary response 88 in murine mammary carcinomas and thus affect cell viability and metastasis (50). CCL2 was revealed to be involved in visfatin-mediated lung cancer NCI-H446 cells transendothelial migration and visfatin-induced CCL2 was attenuated by a specific inhibitor of PI3K/AKT signaling (51).…”

Section: Discussionmentioning

confidence: 99%

CCL2 influences the sensitivity of lung cancer A549 cells to docetaxel

et al. 2018

View full text Add to dashboard Cite

Abstract. Lung cancer is one of the most common malignant tumor types globally. Acquisition of chemoresistance in lung cancer cells is the primary cause of chemotherapy failure. Inflammatory chemokine C-C motif chemokine ligand 2 (CCL2) has been reported to be involved in the progression of cancer and drug resistance. However, its function in docetaxel (DTX) resistance of lung cancer remains unclear. In the present study, the mechanism underlying DTX-induced drug resistance was investigated. Reverse transcription-quantitative polymerase chain reaction and western blot analysis revealed that DTX treatment increased the mRNA and protein expression of CCL2 in lung cancer A549 cells. CCL2 was knocked down by small interfering RNA or was overexpressed by recombinant CCL2 lentivirus, and cell viability was determined. An MTT assay indicated that CCL2 downregulation decreased the viability of A549 cells and augmented the DTX-induced cytotoxicity, whereas CCL2 upregulation protected A549 cells from DTX-induced cytotoxicity. Additionally, it was revealed that CCL2 overexpression activated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling and inhibited apoptosis-associated protein caspase-3 activation and B-cell lymphoma 2 (Bcl-2) phosphorylation at Ser 70 induced by DTX, and enhanced DTX-induced Bcl-2-associated death promoter phosphorylation at Ser 112 . PI3K/AKT inhibitor LY294002 restored DTX-induced caspase-3 activation and Bcl-2 phosphorylation, reversed the effect of CCL2 on the viability of A549 cells and enhanced DTX-induced cytotoxicity. These results demonstrated that chemoresistance may be mediated by cell stress responses involving CCL2 expression, suggesting that CCL2 may be a potential target for enhancing the therapeutic effect of DTX in lung cancer.

show abstract

“…Several studies on tumor cell lines showed that TLR4 stimulation facilitates cell proliferation (4,5). Similarly, LPS facilitates carcinogenesis in mouse models of skin cancer (6), lung cancer (7), breast cancer (8), and colon cancer (9).…”

mentioning

confidence: 99%

Plasmacytoid Dendritic Cells Play a Key Role in Tumor Progression in Lipopolysaccharide-Stimulated Lung Tumor–Bearing Mice

Rega

Terlizzi

Luciano

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

The antitumor activity of LPS was first described by Dr. William Coley. However, its role in lung cancer remains unclear. The aim of our study was to elucidate the dose-dependent effects of LPS (0.1–10 μg/mouse) in a mouse model of B16-F10–induced metastatic lung cancer. Lung tumor growth increased at 3 and 7 d after the administration of low-dose LPS (0.1 μg/mouse) compared with control mice. This was associated with an influx of plasmacytoid dendritic cells (pDCs), regulatory T cells, myeloid-derived suppressor cells, and CD8+ regulatory T cells. In contrast, high-dose LPS (10 μg/mouse) reduced lung tumor burden and was associated with a greater influx of pDCs, as well as a stronger Th1 and Th17 polarization. Depletion of pDCs during low-dose LPS administration resulted in a decreased lung tumor burden. Depletion of pDCs during high-dose LPS treatment resulted in an increased tumor burden. The dichotomy in LPS effects was due to the phenotype of pDCs, which were immunosuppressive after the low-dose LPS, and Th1- and T cytotoxic–polarizing cells after the high-dose LPS. Adoptive transfer of T cells into nude mice demonstrated that CD8+ T cells were responsible for pDC recruitment following low-dose LPS administration, whereas CD4+ T cells were required for pDC influx after the high-dose LPS. In conclusion, our data suggest differential effects of low-dose versus high-dose LPS on pDC phenotype and tumor progression or regression in the lungs of mice.

show abstract

Growth, metastasis, and expression of CCL2 and CCL5 by murine mammary carcinomas are dependent upon Myd88

Cited by 24 publications

References 26 publications

TLR signaling adaptor protein MyD88 in primary sensory neurons contributes to persistent inflammatory and neuropathic pain and neuroinflammation

TLR signaling adaptor protein MyD88 in primary sensory neurons contributes to persistent inflammatory and neuropathic pain and neuroinflammation

CCL2 influences the sensitivity of lung cancer A549 cells to docetaxel

Plasmacytoid Dendritic Cells Play a Key Role in Tumor Progression in Lipopolysaccharide-Stimulated Lung Tumor–Bearing Mice

Contact Info

Product

Resources

About