Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/22754
Title: The CD151-midkine pathway regulates the immune microenvironment in inflammatory breast cancer.
Authors: Hayward, Steven;Gachehiladze, Mariam;Badr, Nahla;Andrijes, Regina;Molostvov, Guerman;Paniushkina, Liliia;Sopikova, Barbora;Slobodová, Zuzana;Mgebrishvili, Giorgi;Sharma, Nisha;Horimoto, Yoshiya;Burg, Dominic;Robertson, Graham;Hanby, Andrew;Hoar, Fiona;Rea, Daniel;Eckhardt, Bedrich L;Ueno, Naoto T;Nazarenko, Irina;Long, Heather M;van Laere, Steven;Shaaban, Abeer M;Berditchevski, Fedor
Affiliation: Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham, UK
Department of Pathology, Menoufia University School of Medicine, Menoufia, Egypt
Department of Clinical and Molecular Pathology, Palacky Univerzity, Olomouc, Czech Republic
Lyramid, 2/55 Clarence St, Sydney, Australia
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Institute for Infection Prevention and Hospital Epidemiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
German Cancer Consortium (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany
Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham, UK
Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham, UK..
Institute for Infection Prevention and Hospital Epidemiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
Department of Clinical and Molecular Pathology, Palacky Univerzity, Olomouc, Czech Republic
Breast Unit, Level 1 Chancellor Wing, St James Hospital, Leeds Teaching Hospitals NHS Trust
Department of Breast Surgical Oncology, Juntendo University School of Medicine, Tokyo, Japan
University of Leeds, Leeds Institute of Cancer and Pathology (LICAP) Leeds..
Department of General and Breast Surgery, Hospital, Sandwell and West Birmingham Hospitals, Birmingham, UK
Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgbaston, Birmingham, UK
Translational Cancer Research Unit Center for Oncological Research, University Antwerp, Belgium
Issue Date: 4-Mar-2020
EDate: 2020-03-04
Citation: The Journal of pathology 2020; online first: 4 March
Abstract: 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. Importantly, elevated expression of CD151 and 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. This article is protected by copyright. All rights reserved.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22754
DOI: 10.1002/path.5415
ORCID: 0000-0002-2633-1161
0000-0003-0911-834X
0000-0002-3402-3900
PubMed URL: 32129471
Type: Journal Article
Subjects: IBC
macrophages
midkine
tetraspanins
tumour microenvironment
Appears in Collections:Journal articles

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