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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
The CD151-midkine pathway regulates the immune microenvironment in inflammatory breast cancer
Journal of Pathology, Volume 251, No. 1, Year 2020
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Description
The immune microenvironment in inflammatory breast cancer (IBC) is poorly characterised, and molecular and cellular pathways that control accumulation of various immune cells in IBC tissues remain largely unknown. Here, we discovered a novel pathway linking the expression of the tetraspanin protein CD151 in tumour cells with increased accumulation of macrophages in cancerous tissues. It is notable that elevated expression of CD151 and a higher number of tumour-infiltrating macrophages correlated with better patient responses to chemotherapy. Accordingly, CD151-expressing IBC xenografts were characterised by the increased infiltration of macrophages. In vitro migration experiments demonstrated that CD151 stimulates the chemoattractive potential of IBC cells for monocytes via mechanisms involving midkine (a heparin-binding growth factor), integrin α6β1, and production of extracellular vesicles (EVs). Profiling of chemokines secreted by IBC cells demonstrated that CD151 increases production of midkine. Purified midkine specifically stimulated migration of monocytes, but not other immune cells. Further experiments demonstrated that the chemoattractive potential of IBC-derived EVs is blocked by anti-midkine antibodies. These results demonstrate for the first time that changes in the expression of a tetraspanin protein by tumour cells can affect the formation of the immune microenvironment by modulating recruitment of effector cells to cancerous tissues. Therefore, a CD151-midkine pathway can be considered as a novel target for controlled changes of the immune landscape in IBC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Authors & Co-Authors
Hayward, Steven
United Kingdom, Birmingham
University of Birmingham
Gachehiladze, Mariam
Czech Republic, Olomouc
Univerzita Palackého V Olomouci
Badr, Nahla M.
United Kingdom, Birmingham
University of Birmingham
Egypt, Shibin el Kom
Menoufia University Faculty of Medicine
Andrijes, Regina
United Kingdom, Birmingham
University of Birmingham
Molostvov, Guerman
United Kingdom, Birmingham
University of Birmingham
Paniushkina, Liliia
Germany, Freiburg Im Breisgau
Albert Ludwigs Universität Freiburg, Medizinische Fakultät
Sopikova, Barbora
Czech Republic, Olomouc
Univerzita Palackého V Olomouci
Slobodová, Zuzana
Czech Republic, Olomouc
Univerzita Palackého V Olomouci
Mgebrishvili, Giorgi
Czech Republic, Olomouc
Univerzita Palackého V Olomouci
Sharma, Nisha
United Kingdom, Leeds
St James's University Hospital
Horimoto, Yoshiya
Japan, Tokyo
Juntendo University School of Medicine
Burg, Dominic
Australia, Sydney
Lyramid Limited
Robertson, Graham
Australia, Sydney
Lyramid Limited
Hanby, Andrew Malcolm
United Kingdom, Leeds
University of Leeds, School of Medicine
Hoar, Fiona
United Kingdom, West Bromwich
Sandwell and West Birmingham Hospitals Nhs Trust
Rea, Daniel William
United Kingdom, Birmingham
University of Birmingham
Eckhardt, Bedrich L.
Australia, Melbourne
Olivia Newton-john Cancer Research Institute
United States, Houston
The University of Texas Md Anderson Cancer Center
United States, Houston
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic
Ueno, Naoto Tada
United States, Houston
The University of Texas Md Anderson Cancer Center
United States, Houston
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic
Nazarenko, Irina
Germany, Freiburg Im Breisgau
Albert Ludwigs Universität Freiburg, Medizinische Fakultät
Germany, Heidelberg
German Cancer Research Center
Long, Heather M.
United Kingdom, Birmingham
University of Birmingham
van Laere, Steven J.
Belgium, Antwerpen
Universiteit Antwerpen
Shaaban, Abeer M.
United Kingdom, Birmingham
University of Birmingham
Berditchevski, Fedor
United Kingdom, Birmingham
University of Birmingham
Statistics
Citations: 23
Authors: 23
Affiliations: 14
Identifiers
Doi:
10.1002/path.5415
ISSN:
00223417
e-ISSN:
10969896
Research Areas
Cancer
Health System And Policy