Prognostic significance of TRAIL-R3 and CCR-2 expression in tumor epithelial cells of patients with early breast cancer

Labovsky, Vivian; Martinez, Leandro Marcelo; Davies, Kevin; Calcagno, María de Luján; García‐Rivello, Hernán; Wernicke, Alejandra; Feldman, Leonardo; Matas, Ayelén; Giorello, María Belén; Borzone, Francisco Raúl; Choi, Hosoon; Howard, Scott C.; Chasseing, Norma Alejandra

doi:10.1186/s12885-017-3259-8

Cited by 17 publications

(11 citation statements)

References 31 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The binding to its receptor CCR2 leads to the differentiation of monocytes into TAMs and to the subsequent promotion of their pro-tumoral activity, tumor cell proliferation, angiogenesis and metastatic dissemination [265,266]. Expression of these chemo-attractants has been linked to worse prognosis in BC patients [267,268,269,270,271] (Table 3). Targeting this axis using CCR2 antagonists and anti-CCL2 antibodies is currently being explored in advanced solid malignancies, including BC (Table 4).…”

Section: Tumor-associated Macrophages and Related Markersmentioning

confidence: 99%

Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy

Chrétien

Zerdes

Bergh

et al. 2019

Cancers

View full text Add to dashboard Cite

Cancer immunotherapy has altered the management of human malignancies, improving outcomes in an expanding list of diseases. Breast cancer - presumably due to its perceived low immunogenicity - is a late addition to this list. Furthermore, most of the focus has been on the triple negative subtype because of its higher tumor mutational load and lymphocyte-enriched stroma, although emerging data show promise on the other breast cancer subtypes as well. To this point the clinical use of immunotherapy is limited to the inhibition of two immune checkpoints, Programmed Cell Death Protein 1 (PD-1) and Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4). Consistent with the complexity of the regulation of the tumor – host interactions and their lack of reliance on a single regulatory pathway, combinatory approaches have shown improved efficacy albeit at the cost of increased toxicity. Beyond those two checkpoints though, a large number of co-stimulatory or co-inhibitory molecules play major roles on tumor evasion from immunosurveillance. These molecules likely represent future targets of immunotherapy provided that the promise shown in early data is translated into improved patient survival in randomized trials. The biological role, prognostic and predictive implications regarding breast cancer and early clinical efforts on exploiting these immune-related therapeutic targets are herein reviewed.

show abstract

Section: Tumor-associated Macrophages and Related Markersmentioning

confidence: 99%

Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy

Chrétien

Zerdes

Bergh

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…The TRAIL apoptotic process occurs by its binding to death receptors but the competitive interaction with decoy receptors 1 ( DcR1 / TRAILR3 / TNFRSF10C ) and 2 ( DcR2 / TRAILR4 / TNFRSF10D ) can induce an inhibitory effect [ 72 ]. The overexpression of TNFRSF10D was shown to be able to protect cells against apoptosis and its expression was associated with BC risk [ 74 , 75 ]. Furthermore, aberrant promoter methylation of TRAIL decoy receptors can be affected by DNMT3A which can be a direct target of microRNAs [ 76 , 77 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of mRNA and miRNA profiles revealed the role of miR-193 and miR-210 as potential regulatory biomarkers in different molecular subtypes of breast cancer

et al. 2021

View full text Add to dashboard Cite

Background Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA (miRNA) expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated. Methods The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex assay, flow cytometry and transwell inserts were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively. Results The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential regulated downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a known mediator on invasion and metastasis, and the tumor suppressor gene RUNX3. Conclusions In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have a specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers

show abstract

“…Experimental data in mouse models show RANKL blockade using OPG-Fc reduced formation of breast cancer metastases [ 20 – 22 ]. In studies in breast cancer patients, most reported either no or an inverse association between tumor RANKL or OPG expression and risk of death [ 23 – 27 ], recurrence [ 23 – 25 , 27 , 28 ], and metastasis [ 25 , 29 , 30 ], though this was not observed in all studies [ 31 ]. Our observation of higher risk of mortality following a breast cancer diagnosis in women with high circulating concentrations of OPG runs counter to these findings on expression in breast cancer tissue.…”

Section: Discussionmentioning

confidence: 99%

Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort

et al. 2018

View full text Add to dashboard Cite

BackgroundReceptor activator of nuclear factor kappa-B (RANK)-signaling is involved in tumor growth and spread in experimental models. Binding of RANK ligand (RANKL) to RANK activates signaling, which is inhibited by osteoprotegerin (OPG). We have previously shown that circulating soluble RANKL (sRANKL) and OPG are associated with breast cancer risk. Here we extend these findings to provide the first data on pre-diagnosis concentrations of sRANKL and OPG and risk of breast cancer-specific and overall mortality after a breast cancer diagnosis.MethodsTwo thousand six pre- and postmenopausal women with incident invasive breast cancer (1620 (81%) with ER+ disease) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed-up for mortality. Pre-diagnosis concentrations of sRANKL and OPG were quantified in baseline serum samples using an enzyme-linked immunosorbent assay and electrochemiluminescent assay, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific and overall mortality were calculated using Cox proportional hazards regression models.ResultsEspecially in women with ER+ disease, higher circulating OPG concentrations were associated with higher risk of breast cancer-specific (quintile 5 vs 1 HR 1.77 [CI 1.03, 3.04]; ptrend 0.10) and overall mortality (q5 vs 1 HR 1.39 [CI 0.94, 2.05]; ptrend 0.02). sRANKL and the sRANKL/OPG ratio were not associated with mortality following a breast cancer diagnosis.ConclusionsHigh pre-diagnosis endogenous concentrations of OPG, the decoy receptor for RANKL, were associated with increased risk of death after a breast cancer diagnosis, especially in those with ER+ disease. These results need to be confirmed in well-characterized patient cohorts.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4887-3) contains supplementary material, which is available to authorized users.

show abstract

Prognostic significance of TRAIL-R3 and CCR-2 expression in tumor epithelial cells of patients with early breast cancer

Cited by 17 publications

References 31 publications

Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy

Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy

Integrated analysis of mRNA and miRNA profiles revealed the role of miR-193 and miR-210 as potential regulatory biomarkers in different molecular subtypes of breast cancer

Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort

Contact Info

Product

Resources

About