NDLI: Positive lymph-node breast cancer patients activation of NF-κB in tumor-associated leukocytes stimulates cytokine secretion that promotes metastasis via C-C chemokine receptor CCR7.

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Positive lymph-node breast cancer patients activation of NF-κB in tumor-associated leukocytes stimulates cytokine secretion that promotes metastasis via C-C chemokine receptor CCR7.

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Positive lymph-node breast cancer patients activation of NF-κB in tumor-associated leukocytes stimulates cytokine secretion that promotes metastasis via C-C chemokine receptor CCR7.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	El-Ghonaimy, Eslam A. El-Shinawi, Mohamed Ibrahim, Sherif A. El-Ghazaly, Hisham Abd-El-Tawab, Reda Nouh, Mohamed A. El-Mamlouk, Tahani Mohamed, Mona M.
Description	Country affiliation: Egypt Author Affiliation: El-Ghonaimy EA ( Department of Zoology, Cairo University, Giza, Egypt.)
Abstract	Tumor metastasis to lymph nodes is most deadly complication among breast cancer patients. Herein, we investigated the molecular mechanism by which tumor-associated leukocytes (TALs) mediate lymph node metastasis. The density of different leukocyte subtypes infiltrating the tumor microenvironment of negative and positive lymph nodes (nLNs, pLNs) in breast cancer patients was measured using immunohistochemistry. In addition, we isolated TALs from blood drained from the axillary tributaries of nLN and pLN patients during breast surgery. Secretions of TALs were subjected to cytokine profiling using a cytokine antibody array. Our results showed an increase in the number of infiltrated CD45+ cells in the carcinoma tissues of pLN patients with the major proportion being myeloid subsets compared with nLN patients. Furthermore, TALs of pLN patients show a significant fivefold increase in the secretion of interleukin (IL)-1 , interferon-Î³, IL-5, IL-3 and tumor necrosis factor-ß, and are characterized by enhanced constitutive NF-κB/p65 signaling compared with TALs isolated from nLN patients. Using an invasion assay, cytokines secreted by TALs of pLN patients were shown to augment the invasive phenotype of breast cancer MCF-7 and SKBR3 cells compared with nLN patients. Using flow cytometry, we found that C-C chemokine receptor 7 (CCR7) is significantly overexpressed in breast carcinoma of pLN patients compared with nLNs patients. Intriguingly, CCR7, a mechanistic clue for metastasis, is upregulated in MCF-7 cells upon stimulation with TAL-conditioned media of pLN patients. Our findings show that the molecular cues secreted by TALs alone or in combination with CCR7 may emerge as future therapeutic targets for lymph node metastasis in breast cancer patients.
File Format	HTM / HTML
ISSN	1742464X
Issue Number	2
Volume Number	282
e-ISSN	17424658
Journal	FEBS Journal
Language	English
Publisher	Wiley (on behalf of the Federation of European Biochemical Societies)
Publisher Date	2015-01-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Biochemistry Breast Neoplasms Genetics Leukocytes Metabolism Nf-kappa B Receptors, Ccr7 Biosynthesis Aged Antigens, Cd45 Pathology Female Flow Cytometry Humans Lymph Nodes Immunology Mcf-7 Cells Middle Aged Neoplasm Metastasis Tumor Microenvironment Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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Positive lymph-node breast cancer patients ­ activation of NF-κB in tumor-associated leukocytes stimulates cytokine secretion that promotes metastasis via C-C chemokine receptor CCR7.

Positive lymph-node breast cancer patients activation of NF-κB in tumor-associated leukocytes stimulates cytokine secretion that promotes metastasis via C-C chemokine receptor CCR7.