CXCR3, a double-edged sword in tumor progression and angiogenesis

Billottet, Clotilde; Quemener, Cathy; Bikfalvi, Andréas

doi:10.1016/j.bbcan.2013.08.002

Cited by 107 publications

(142 citation statements)

References 82 publications

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“…4). 13,24 CXCL9 and CXCL10, the two most upregulated genes in our analysis, both have important pro-tumor roles [114][115][116][117] and can both be activated by the transcription factor NF-kb, as suggested in our model (Fig. 4).…”

Section: Cross-talk Between Transcription Factors Cytokines and Aqpssupporting

confidence: 60%

Role of aquaporins in cell proliferation: What else beyond water permeability?

2016

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In addition to the extensive data demonstrating the importance of mammalian AQPs for the movement of water and some small solutes across the cell membrane, there is now a growing body of evidence indicating the involvement of these proteins in numerous cellular processes seemingly unrelated, at least some of them in a direct way, to their canonical function of water permeation. Here, we have presented a broad range of evidence demonstrating that these proteins have a role in cell proliferation by various different mechanisms, namely, by allowing fast cell volume regulation during cell division; by affecting progression of cell cycle and helping maintain the balance between proliferation and apoptosis, and by crosstalk with other cell membrane proteins or transcription factors that, in turn, modulate progression of the cell cycle or regulate biosynthesis pathways of cell structural components. In the end, however, after discussing all these data that strongly support a role for AQPs in the cell proliferation process, it remains impossible to conclude that all these other functions attributed to AQPs occur completely independently of their water permeability, and there is a need for new experiments designed specifically to address this interesting issue.

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Section: Cross-talk Between Transcription Factors Cytokines and Aqpssupporting

confidence: 60%

Role of aquaporins in cell proliferation: What else beyond water permeability?

2016

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“…In addition, EGFR (also known as ERBB1) and ERBB3, found in these lesions, are part of the ErbB family, which has been shown to be critical for Schwann cell differentiation and survival (52). Genes involved in cell death included TNFSF10 (also know as TRAIL), CXCR3, CCL19, and IDO, which regulate apoptosis (53)(54)(55)(56), consistent with the prominent apoptosis present in RR lesions in comparison to nonreactional patients (57,58). We previously demonstrated that M. leprae ligands induce apoptosis of Schwann cells through TLR2, providing one mechanism by which activation of the innate immune response contributes to nerve injury in leprosy (59).…”

Section: Discussionmentioning

confidence: 99%

Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy

Inkeles¹,

Teles²,

Pouldar³

et al. 2016

JCI Insight

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“…Paired analysis of mRNAs and proteins in tissue and serum might provide evidence to resolve this discrepancy. As CXCL11 has distinct immunoregulatory functions, in contrast to immunostimulatory functions mediated by CXCL9 and CXCL10 (24,25), we prefer the following nonmutually exclusive explanations of how CXCL11, even in the presence of CXCL9 and CXCL10, may limit T-cell effector function as a part of negative feedback loop: (i) disrupting chemokine gradients for directional migration of T cells (26), (ii) preventing CXCR3-CXCL9/10 interaction by promoting receptor internalization (24), (iii) suppressing T-cell responses through induction and/or recruitment of regulatory T cells (25,27), and (iv) promoting growth and metastasis of tumors expressing CXCR3 (28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Serum Immunoregulatory Proteins as Predictors of Overall Survival of Metastatic Melanoma Patients Treated with Ipilimumab

et al. 2015

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Treatment with ipilimumab improves overall survival (OS) in patients with metastatic melanoma. Because ipilimumab targets T lymphocytes and not the tumor itself, efficacy may be uniquely sensitive to immunomodulatory factors present at the time of treatment. We analyzed serum from patients with metastatic melanoma (247 of 273, 90.4%) randomly assigned to receive ipilimumab or gp100 peptide vaccine. We quantified candidate biomarkers at baseline and assessed the association of each using multivariate analyses. Results were confirmed in an independent cohort of similar patients (48 of 52, 92.3%) treated with ipilimumab. After controlling for baseline covariates, elevated chemokine (C-X-C motif) ligand 11 (CXCL11) and soluble MHC class I polypeptide-related chain A (sMICA) were associated with poor OS in ipilimumab-treated patients [log 10 CXCL11: HR, 1.88; 95% confidence interval (CI), 1.14-3.12; P ¼ 0.014; and log 10 sMICA quadratic effect P ¼ 0.066; sMICA (! 247 vs. 247): HR, 1.75; 95% CI, 1.02-3.01]. Multivariate analysis of an independent ipilimumab-treated cohort confirmed the association between log 10 CXCL11 and OS (HR, 3.18; 95% CI, 1.13-8.95; P ¼ 0.029), whereas sMICA was less strongly associated with OS [log 10 sMICA quadratic effect P ¼ 0.16; sMICA (!247 vs. 247): HR, 1.48; 95% CI, 0.67-3.27]. High baseline CXCL11 and sMICA were associated with poor OS in patients with metastatic melanoma after ipilimumab treatment but not vaccine treatment. Thus, pretreatment CXCL11 and sMICA may represent predictors of survival benefit after ipilimumab treatment as well as therapeutic targets. Cancer Res; 75(23); 5084-92. Ó2015 AACR.

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CXCR3, a double-edged sword in tumor progression and angiogenesis

Cited by 107 publications

References 82 publications

Role of aquaporins in cell proliferation: What else beyond water permeability?

Role of aquaporins in cell proliferation: What else beyond water permeability?

Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy

Serum Immunoregulatory Proteins as Predictors of Overall Survival of Metastatic Melanoma Patients Treated with Ipilimumab

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