scholarly journals MMP1 and MMP11 Expression in Peripheral Blood Mononuclear Cells upon Their Interaction with Breast Cancer Cells and Fibroblasts

2020 ◽  
Vol 22 (1) ◽  
pp. 371
Author(s):  
Noemi Eiro ◽  
Sandra Cid ◽  
Nuria Aguado ◽  
María Fraile ◽  
Nagore de Pablo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Breast Cancer Cells ◽  
Mononuclear Cells ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
The Impact

Tumor-infiltrating immune cells phenotype is associated with tumor progression. However, little is known about the phenotype of the peripheral blood mononuclear cells (PBMC) from breast cancer patients. We investigated MMP1 and MMP11 expression in PBMC from breast cancer patients and we analyzed gene expression changes upon their interaction with cancer cells and cancer-associated fibroblasts (CAF). We measured the impact of PBMC on proinflammatory gene expression in breast cancer cells, normal fibroblast (NF), and CAF and the impact on proliferation and invasiveness capacity of breast cancer cells. Gene expression of MMP1 and MMP11 in PBMC from breast cancer patients (n = 54) and control (n = 28); expression of IL1A, IL6, IL17, IFNβ, and NFĸB in breast cancer cell lines (MCF-7 and MDA-MB-231); and, additionally, IL10 and MMP11 in CAF and NF were analyzed by qRT-PCR before and after co-culture. Our results show the existence of a subpopulation of breast cancer patients (25.9%) with very high levels of MMP11 gene expression in PBMC. Also, gene expression of MMP1 and MMP11 increases in PBMC after co-culture with breast cancer cell lines, NF or CAF. PBMC from healthy or breast cancer patients induce an increased proliferation rate on MCF-7 and an increased invasiveness capacity of MDA-MB-231. Finally, we show a differential expression profile of inflammatory genes in NF and CAF when co-cultured with control or breast cancer PBMC. We have observed that MMPs’ expression in PBMC is regulated by the microenvironment, while the expression of inflammatory genes in NF or CAF is differentially regulated by PBMC. These findings confirm the importance of the crosstalk between stromal cells and suggest that PBMC would play a role in promoting aggressive tumor behavior.

Noninvasive identification of lineage-specific circular RNA for ER-positive breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3543-3543 ◽  
Author(s):  
Jason Brown ◽  
Palak Shah ◽  
Josh Vo ◽  
Lanbo Xiao ◽  
Yashar Niknafs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Breast Cancer Cells ◽  
Circular Rna ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Non Invasive ◽  
Er Positive ◽  
Positive Breast Cancer

3543 Background: Non-invasive testing in plasma using RNA biomarkers has been limited by exoribonuclease-mediated degradation of RNA. Circular RNA (circRNA) are covalently closed RNA structures that resist this degradation due to their circular structure. Therefore circRNA are more stable than their linear counterparts. CircRNA are formed by alternative backsplicing of the 3’ end of a downstream exon to the 5’ end of an upstream exon. Here, we propose a novel method for non-invasive identification of circRNA and demonstrate circularized forms of several lineage and cancer specific targets for estrogen receptor-positive breast cancer. Methods: Capture RNA sequencing on cancer tissue was previously performed to determine the relative expression of potential circRNA isoforms in breast cancer patients. These isoforms as well as those predicted by intron length were screened using a quantitative PCR-based assay on ER-positive breast cancer cells. RNA extracted from breast cancer cells are exposed to ribonuclease R to demonstrate stability of circRNA. CircRNA derived from targets with known universal expression are used as positive controls as well as for analysis on plasma. Results: We identify the circRNA isoforms with highest expression for five genes, including ESR1, that are differentially expressed in ER-positive breast cancer compared to other cancers and normal breast tissue. We determine that the circRNA corresponding to all five targets is specifically expressed in breast cancer cell lines with at least 1000-fold higher expression than in non-ER positive breast cancer cell lines. We demonstrate that the highest expressing circRNA isoforms are resistant to degradation by ribonuclease R, whereas corresponding linear mRNA is susceptible. We also demonstrate the presence and stability of positive control circRNA in plasma from patients without cancer. Conclusions: CircRNA are promising biomarkers for early non-invasive detection of cancer due to their stability in plasma. This assay reliably detects ER-positive breast cancer specific circRNA, and exoribonuclease resistance has been validated. Application of this diagnostic assay to plasma from breast cancer patients is underway.

scholarly journals Hyperglycaemia-induced chemoresistance in breast cancer cells: role of the estrogen receptor

2015 ◽  
Vol 23 (2) ◽  
pp. 125-134 ◽  
Author(s):  
L Zeng ◽  
H A Zielinska ◽  
A Arshad ◽  
J P Shield ◽  
A Bahl ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Breast Cancer Cells ◽  
Diabetic Patients ◽  
Breast Cancer Patients ◽  
Patients With Diabetes ◽  
The Impact ◽  
Positive Breast Cancer

Breast cancer patients with diabetes respond less well to chemotherapy; in keeping with this we determined previously that hyperglycaemia-induced chemoresistance in estrogen receptor (ERα) positive breast cancer cells and showed that this was mediated by fatty acid synthase (FASN). More recent evidence suggests that the effect of metabolic syndrome and diabetes is not the same for all subtypes of breast cancer with inferior disease-free survival and worse overall survival only found in women with ERα positive breast cancer and not for other subtypes. Here we examined the impact of hyperglycaemia on ERα negative breast cancer cells and further investigated the mechanism underlying chemoresistance in ERα with a view to identifying strategies to alleviate hyperglycaemia-induced chemoresistance. We found that hyperglycaemia-induced chemoresistance was only observed in ERα breast cancer cells and was dependent upon the expression of ERα as chemoresistance was negated when the ERα was silenced. Hyperglycaemia-induced an increase in activation and nuclear localisation of the ERα that was downstream of FASN and dependent on the activation of MAPK. We found that fulvestrant successfully negated the hyperglycaemia-induced chemoresistance, whereas tamoxifen had no effect. In summary our data suggests that the ERα may be a predictive marker of poor response to chemotherapy in breast cancer patients with diabetes. It further indicates that anti-estrogens could be an effective adjuvant to chemotherapy in such patients and indicates the importance for the personalised management of breast cancer patients with diabetes highlighting the need for clinical trials of tailored chemotherapy for diabetic patients diagnosed with ERα positive breast cancers.

scholarly journals MMP1 and MMP11 expression in Peripheral Blood Mononuclear Cells upon their interaction with Breast Cancer Cells and Fibroblasts

2020 ◽  
Author(s):  
Noemi Eiro ◽  
Sandra Cid ◽  
Nuria Aguado ◽  
María Fraile ◽  
Jorge Rubén Cabrera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Inflammatory Genes

Abstract Background: Tumor-infiltrating immune cells phenotype is associated with tumor progression. However, little is known about the phenotype of the Peripheral Blood Mononuclear Cells (PBMC) from breast cancer patients. Here, we investigated the expression of MMP1 and MMP11 in PBMC from breast cancer patients and we analyzed gene expression changes upon their interaction with cancer cells and Cancer-Associated Fibroblasts (CAF). Finally, we measured the impact of PBMC in proinflammatory genes expression in normal fibroblast and CAF.Results: Gene expression of MMP1 and MMP11 in PBMC from breast cancer patients (n=54) and control (n=28), and expression of IL1A, IL6, IL17, IFNβ and NFB in breast cancer cell lines (MCF-7 and MDA-MB-231), CAF and in Normal Fibroblasts (NF) were analyzed by qRT-PCR before and after co-culture. Our results show the existence of a group of breast cancer patients (25.9%) with very high levels of MMP11 gene expression in PBMC. Also, we present evidence of increased gene expression of MMP1 and MMP11 in PBMC after co-culture with breast cancer cell lines, NF or CAF. Finally, we show a differential expression profile of inflammatory genes in NF and CAF when co-cultured with control or breast cancer PBMC.Conclusions: We have observed that MMPs expression in PBMC is regulated by the microenvironment, while the expression of inflammatory genes in NF or CAF is differentially regulated by control or breast cancer PBMC. These findings confirm the importance of the interaction and communication between stromal cells and suggest that PBMC would play a role to promote an aggressive tumor behavior.

scholarly journals Reduced IQGAP2 expression promotes EMT and inhibits apoptosis by modulating the MEK-ERK and p38 signaling in breast cancer irrespective of ER status

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Dinesh Kumar ◽  
Saket Awadesbhai Patel ◽  
Md. Khurshidul Hassan ◽  
Nachiketa Mohapatra ◽  
Niharika Pattanaik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Breast Cancer Cells ◽  
Xenograft Model ◽  
Breast Cancer Cell Lines ◽  
Dependent Manner ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Erk Activation

AbstractIQGAP2, a member of the IQGAP family, functions as a tumor suppressor in most of the cancers. Unlike IQGAP1 and IQGAP3, which function as oncogenes in breast cancer, the role of IQGAP2 is still unexplored. Here we report a reduced expression of IQGAP2, which was associated with lymph node positivity, lymphovascular invasion, and higher age in breast cancer patients. We found an inverse correlation of IQGAP2 expression levels with oncogenic properties of breast cancer cell lines in estrogen receptor (ER) independent manner. IQGAP2 expression enhanced apoptosis via reactive oxygen species (ROS)-P38-p53 pathway and reduced epithelial–mesenchymal transition (EMT) in a MEK-ERK-dependent manner. IQGAP2-IQGAP1 ratio correlated negatively with phospho-ERK levels in breast cancer patients. Pull-down assay showed interaction of IQGAP1 and IQGAP2. IQGAP2 overexpression rescued, IQGAP1-mediated ERK activation, suggesting the possibility of IQGAP1 sequestration by IQGAP2. IQGAP2 depletion, in a tumor xenograft model, increased tumor volume, tumor weight, and phospho-ERK expression. Overall, our findings suggest that IQGAP2 is negatively associated with proliferative and metastatic abilities of breast cancer cells. Suppression of IQGAP1-mediated ERK activation is a possible route via which IQGAP2 restricts oncogenic properties of breast cancer cells. Our study highlights the candidature of IQGAP2 as a potent target for therapeutic intervention.

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