The CD151‐midkine pathway regulates the immune microenvironment in inflammatory breast cancer

• DOI: 10.1002/path.5415
• Publication Date: 2020-03-04T10:54:49Z
• Authors: Steven Hayward; Mariam Gachehiladze; Nahla Badr; Regina Andrijes; Guerman Molostvov; Liliia Paniushkina; Barbora Sopikova; Zuzana Slobodová; Giorgi Mgebrishvili; Nisha Sharma; Yoshiya Horimoto; Dominic Burg; Graham Robertson; Andrew Hanby; Fiona Hoar; Daniel Rea; Bedrich L Eckhardt; Naoto T Ueno; Irina Nazarenko; Heather M Long; Steven van Laere; Abeer M Shaaban; Fedor Berditchevski
• Keywords: Midkine; Tetraspanin

Abstract The immune microenvironment in inflammatory breast cancer (IBC) is poorly characterised, and molecular cellular pathways that control accumulation of various cells IBC tissues remain largely unknown. Here, we discovered a novel pathway linking the expression tetraspanin protein CD151 tumour with increased macrophages cancerous tissues. It notable elevated higher number tumour‐infiltrating correlated better patient responses to chemotherapy. Accordingly, CD151‐expressing xenografts were characterised by infiltration macrophages. In vitro migration experiments demonstrated stimulates chemoattractive potential for monocytes via mechanisms involving midkine (a heparin‐binding growth factor), integrin α6β1, production extracellular vesicles (EVs). Profiling chemokines secreted increases midkine. Purified specifically stimulated monocytes, but not other cells. Further IBC‐derived EVs blocked anti‐midkine antibodies. These results demonstrate first time changes can affect formation modulating recruitment effector Therefore, CD151‐midkine be considered as target controlled landscape IBC. © 2020 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.