| Title |
Secretome of tumor-associated leukocytes augment epithelial-mesenchymal transition in positive lymph node breast cancer patients via activation of EGFR/Tyr845 and NF-κB/p65 signaling pathway
|
|---|---|
| Published in |
Tumor Biology, June 2016
|
| DOI | 10.1007/s13277-016-5123-x |
| Pubmed ID | |
| Authors |
Eslam A. Elghonaimy, Sherif A. Ibrahim, Amal Youns, Zeinab Hussein, Mohamed Akram Nouh, Tahani El-mamlouk, Mohamed El-Shinawi, Mona Mostafa Mohamed |
| Abstract |
Epithelial-mesenchymal transition (EMT) is an essential process in breast cancer metastasis. The aim of the present study was to determine the role of secretions of tumor-associated leukocytes (TALs) isolated from negative and positive lymph nodes (nLNs and pLNs, respectively) breast cancer patients in regulating EMT mechanism and the associated signaling pathways. We found an increased infiltration of TALs, which was associated with downregulation of E-cadherin and over-expression of vimentin in the breast carcinoma tissues of pLNs as compared to nLNs patients and normal breast tissues obtained from healthy volunteers during mammoplasty. Furthermore, TALs isolated from pLNs breast cancer patients secreted an elevated panel of cytokines by up to 2-5-fold when compared with those isolated from nLNs patients. Secretome of TALs of pLNs possessed higher TARC, IGF-1, IL-3, TNF-β, IL-5, G-CSF, IL-4, and IL-1α with more than a fivefold compared to those of nLNs. Using the human breast cancer cell lines MCF-7 and MDA-MB-231, we found that cytokines secreted by TALs isolated from nLNs and pLNs breast cancer patients promoted EMT via upregulation of TGF-β and vimentin and downregulation of E-cadherin at messenger RNA (mRNA) levels in both cell lines and at protein level in MCF-7. While TGF-β is over-expressed by MDA-MB-231 seeded in media conditioned by secretome of TALs isolated from nLNs and pLNs breast cancer patients. The downstream TGF-β signaling transcription factors, Snail, Slug, and Twist, known to be associated with EMT mechanism were over-expressed by MCF-7 and MDA-MB-231 seeded in media conditioned by secretome of TALs isolated from nLNs and pLNs breast cancer patients. Acquisition of EMT in MCF-7 cells is mechanistically attributed to the activation of EGFR((Tyr845)) and NF-κB/p65((Ser276)) signaling which are significantly highly expressed by MCF-7 cells seeded in media conditioned by secretome of TALs isolated from pLNs compared to nLNs patients. Overall, this study provides implications of secretome of TALs and activated EGFR((Tyr845)) and NF-κB/p65((Ser276)) in EMT process that may be considered a therapeutic strategy to inhibit lymph node metastasis in breast cancer patients. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 36 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 14% |
| Student > Master | 5 | 14% |
| Student > Bachelor | 4 | 11% |
| Student > Ph. D. Student | 4 | 11% |
| Professor | 3 | 8% |
| Other | 5 | 14% |
| Unknown | 10 | 28% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 31% |
| Biochemistry, Genetics and Molecular Biology | 7 | 19% |
| Agricultural and Biological Sciences | 3 | 8% |
| Sports and Recreations | 3 | 8% |
| Immunology and Microbiology | 1 | 3% |
| Other | 2 | 6% |
| Unknown | 9 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 June 2016.
All research outputs
#18,464,797
of 22,879,161 outputs
Outputs from Tumor Biology
#1,370
of 2,623 outputs
Outputs of similar age
#267,570
of 352,770 outputs
Outputs of similar age from Tumor Biology
#34
of 92 outputs
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