Tumor-Associated Macrophage-Induced Invasion and Angiogenesis of Human Basal Cell Carcinoma Cells by Cyclooxygenase-2 Induction

Tjiu, Jeng-Wei; Chen, Jau-Shiuh; Shun, Chia‐Tung; Lin, Sung‐Jan; Liao, Yi‐Hua; Chu, Chia-Yu; Tsai, Tsen‐Fang; Hc, Chiu; Dai, Yue; Inoue, H.; Yang, Pan‐Chyr; Kuo, Min-Liang; Jee, Shiou‐Hwa

doi:10.1038/jid.2008.310

Cited by 308 publications

(301 citation statements)

References 26 publications

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“…NECA, specific adenosine receptor agonists, and antagonists were used to characterize the effect of adenosine receptor modulation on NR4A1-3 receptor expression in monocytic cell types used in numerous similar studies including primary human PBMCs, THP-1, and murine raw macrophage 264.7 cells (24)(25)(26)(27)(28). PMA was further used to differentiate THP-1 monocytes to an alternative macrophage phenotype (PMA-differentiated THP-1 cells) (29).…”

Section: Resultsmentioning

confidence: 99%

Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells

Crean

Cummins

Bahar

et al. 2015

The Journal of Immunology

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Adenosine receptor–mediated regulation of monocyte/macrophage inflammatory responses is critical in the maintenance of tissue homeostasis. In this study, we reveal that adenosine potently modulates the expression of NR4A1, 2, and 3 orphan nuclear receptors in myeloid cells, and this modulation is primarily through the adenosine A2a receptor subtype. We demonstrate that A2a receptor activation of NR4A1-3 receptor synthesis is further enhanced in TLR4-stimulated monocytes. After TLR4 stimulation, NR4A receptor–depleted monocyte/macrophage cells display significantly altered expression of cell-surface markers and produce increased inflammatory cytokine and chemokine secretion rendering the cells an enhanced proinflammatory phenotype. Exposure of TLR4 or TNF-α–stimulated monocytes to adenosine analogs directs changes in the expression of MIP-3α and IL-23p19, with NR4A2 depletion leading to significantly enhanced expression of these factors. Furthermore, we establish that nuclear levels of NF-κB/p65 are increased in TLR/adenosine-stimulated NR4A2-depleted cells. We show that, after TLR/adenosine receptor stimulation, NR4A2 depletion promotes significant binding of NF-κB/p65 to a κB consensus binding motif within the MIP-3α proximal promoter leading to increased protein secretion, confirming a pivotal role for NF-κB activity in controlling cellular responses and gene expression outcomes in response to these mediators. Thus, these data demonstrate that during an inflammatory response, adenosine modulation of NR4A receptor activity acts to limit NF-κB–mediated effects and that loss of NR4A2 expression leads to enhanced NF-κB activity and hyperinflammatory responses in myeloid cells.

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Section: Resultsmentioning

confidence: 99%

Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells

Crean

Cummins

Bahar

et al. 2015

The Journal of Immunology

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“…Researches have demonstrated that PMA-induced macrophages and M2-polarized macrophages shared the same profile (Tjiu et al, 2009). The phenotype and function of M2-polarized macrophages were very similar to that of TAM (tumor-associated macrophages), but M2-polarized macrophages were still not equaled to TAM (Grivennikov et al, 2010(Grivennikov et al, , 2010Mantovani et al).…”

Section: Il-12 Treatment Increased B7-h1 Expression In Ovarian Cancermentioning

confidence: 99%

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling

Xiong¹,

Ma²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…15 Macrophage polarization was achieved by treating the cultured monocyte-derived macrophages with 20 ng/mL IFN-g and 100 ng/mL of LPS (to induce M1 phenotype), 20 ng/mL IL-4 (to induce M2 phenotype), or no cytokines (subsequently referred to as M0), for 2 d. Relative gene expression was calculated by the 2 ¡DDCT method as previously described. 16 Data were calculated as the fold change in expression of the target gene relative to housekeeping gene (GAPDH).…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

ElevatedARG1expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients

Jung

Sabri

Hanson

et al. 2015

Cancer Biology & Therapy

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Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n D 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines before quantitative analysis of their "M1/M2" activation markers, iNOS, Arg1, and TGFß1. Statistical analysis was performed to correlate experimental data to clinical assessment of acute skin toxicity using Common Toxicity Criteria (CTC) grade for objective evaluation of skin reactions. Increased ARG1 mRNA significantly correlated with higher grades of erythema, moist desquamation, and CTC grade. Multivariate analysis revealed that increased ARG1 expression in macrophages after a single RT dose was an independent prognostic factor of erythema (p D 0 .032), moist desquamation (p D 0 .027), and CTC grade (p D 0 .056). Interestingly, multivariate analysis of ARG1 mRNA expression in macrophages stimulated with IL-4 also revealed independent prognostic value for predicting acute RT-induced toxicity factors, erythema (p D 0 .069), moist desquamation (p D 0 .037), and CTC grade (p D 0 .046). To conclude, our findings underline for the first time the biological significance of increased ARG1 mRNA levels as an early independent predictive biomarker of RT-induced acute skin toxicities.

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Tumor-Associated Macrophage-Induced Invasion and Angiogenesis of Human Basal Cell Carcinoma Cells by Cyclooxygenase-2 Induction

Cited by 308 publications

References 26 publications

Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells

Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells

IL-12 Regulates B7-H1 Expression in Ovarian Cancer-associated Macrophages by Effects on NF-κB Signalling

ElevatedARG1expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients

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