IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients

Macrophage-associated cytokines play an important role in cancer metastasis however the functions of Interleukins (IL) 6 and 10 in breast cancer (BC) progression and metastasis are not clear. In this study the roles of IL-6/IL-10 in regulating vascular invasion and their prognostic significance in B...

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Main Authors: Ahmad, Narmeen, Ammar, Aula, Storr, Sarah J., Green, Andrew R., Rakha, Emad, Ellis, Ian, Martin, Stewart G.
Format: Article
Published: Springer 2018
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Online Access:https://eprints.nottingham.ac.uk/48799/
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author Ahmad, Narmeen
Ammar, Aula
Storr, Sarah J.
Green, Andrew R.
Rakha, Emad
Ellis, Ian
Martin, Stewart G.
author_facet Ahmad, Narmeen
Ammar, Aula
Storr, Sarah J.
Green, Andrew R.
Rakha, Emad
Ellis, Ian
Martin, Stewart G.
author_sort Ahmad, Narmeen
building Nottingham Research Data Repository
collection Online Access
description Macrophage-associated cytokines play an important role in cancer metastasis however the functions of Interleukins (IL) 6 and 10 in breast cancer (BC) progression and metastasis are not clear. In this study the roles of IL-6/IL-10 in regulating vascular invasion and their prognostic significance in BC are investigated. MDA-MB-231 and MCF-7 migration (+/- IL-6 or IL-10) was assessed by scratch wound assay. Cancer cell adhesion to IL-6/IL-10 stimulated blood and lymphatic endothelial cells (EC) was investigated. Expression of IL-6 /IL-10 was assessed using immunohistochemistry in an annotated cohort of early stage BC (n=1380) and associations with clinicopathological variables and clinical outcome evaluated. IL-6 did not alter BC cell migration however a dose-dependent inhibition in MDA-MB-231 migration with IL-10 treatment was observed (P=0.03). BC cells were more adhesive to blood vs lymphatic EC however IL-6/IL-10 had no effect on adhesion patterns. High expression of IL-6/IL-10 was associated with clinicopathological criteria (e.g. hormone receptor status, all P<0.05), improved disease free survival (DFS; P<0.05) and improved BC specific survival (BCSS; only IL-6, P=0.017). However neither IL-6 nor IL-10 expression were independent prognostic factors from multivariate analysis. In BC subgroups, IL-6 and IL-10 were good prognosticators in terms of DFS in non-basal, non-triple negative (non-TN), ER-positive, PgR-positive (only IL-10), and Her-2-negative (only IL-6) BC (all P<0.05). IL-6 was associated with improved BCSS in non-basal, ER-positive and non-TN BC (all P<0.05).
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spelling nottingham-487992024-08-15T15:31:16Z https://eprints.nottingham.ac.uk/48799/ IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients Ahmad, Narmeen Ammar, Aula Storr, Sarah J. Green, Andrew R. Rakha, Emad Ellis, Ian Martin, Stewart G. Macrophage-associated cytokines play an important role in cancer metastasis however the functions of Interleukins (IL) 6 and 10 in breast cancer (BC) progression and metastasis are not clear. In this study the roles of IL-6/IL-10 in regulating vascular invasion and their prognostic significance in BC are investigated. MDA-MB-231 and MCF-7 migration (+/- IL-6 or IL-10) was assessed by scratch wound assay. Cancer cell adhesion to IL-6/IL-10 stimulated blood and lymphatic endothelial cells (EC) was investigated. Expression of IL-6 /IL-10 was assessed using immunohistochemistry in an annotated cohort of early stage BC (n=1380) and associations with clinicopathological variables and clinical outcome evaluated. IL-6 did not alter BC cell migration however a dose-dependent inhibition in MDA-MB-231 migration with IL-10 treatment was observed (P=0.03). BC cells were more adhesive to blood vs lymphatic EC however IL-6/IL-10 had no effect on adhesion patterns. High expression of IL-6/IL-10 was associated with clinicopathological criteria (e.g. hormone receptor status, all P<0.05), improved disease free survival (DFS; P<0.05) and improved BC specific survival (BCSS; only IL-6, P=0.017). However neither IL-6 nor IL-10 expression were independent prognostic factors from multivariate analysis. In BC subgroups, IL-6 and IL-10 were good prognosticators in terms of DFS in non-basal, non-triple negative (non-TN), ER-positive, PgR-positive (only IL-10), and Her-2-negative (only IL-6) BC (all P<0.05). IL-6 was associated with improved BCSS in non-basal, ER-positive and non-TN BC (all P<0.05). Springer 2018-04 Article PeerReviewed Ahmad, Narmeen, Ammar, Aula, Storr, Sarah J., Green, Andrew R., Rakha, Emad, Ellis, Ian and Martin, Stewart G. (2018) IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients. Cancer Immunology, Immunotherapy, 67 (4). pp. 537-549. ISSN 1432-0851 Breast cancer; IL-6; IL-10; Macrophage-associated cytokines; Metastasis https://link.springer.com/article/10.1007%2Fs00262-017-2106-8 doi:10.1007/s00262-017-2106-8 doi:10.1007/s00262-017-2106-8
spellingShingle Breast cancer; IL-6; IL-10; Macrophage-associated cytokines; Metastasis
Ahmad, Narmeen
Ammar, Aula
Storr, Sarah J.
Green, Andrew R.
Rakha, Emad
Ellis, Ian
Martin, Stewart G.
IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients
title IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients
title_full IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients
title_fullStr IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients
title_full_unstemmed IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients
title_short IL-6 and IL-10 are associated with good prognosis in early stage invasive breast cancer patients
title_sort il-6 and il-10 are associated with good prognosis in early stage invasive breast cancer patients
topic Breast cancer; IL-6; IL-10; Macrophage-associated cytokines; Metastasis
url https://eprints.nottingham.ac.uk/48799/
https://eprints.nottingham.ac.uk/48799/
https://eprints.nottingham.ac.uk/48799/