Impact of diet‐derived polyphenol EGCG on neurotensin response upon HL‐60 promyelocytic leukemia cells acquisition of a macrophage‐like phenotype

Abstract

BackgroundThe activation of a neurotensin (NTS)/neurotensin receptor (NTSR) axis in T lymphocytes, macrophages, and dendritic cells suggests that NTS could modulate immune response and trigger prosurvival signaling in malignant human B lymphocytes. Such axis can therefore represent a potential therapeutic target in chronic B cell leukemia.MethodsIn this study, analysis of NTS and NTSR1‐3 expression in acute myeloid leukemia (AML) patients using Kaplan‐Meyer plots specifically highlighted NTS and NTSRs as poor clinical prognosis biomarkers. NTSRs gene and protein expression was also explored in undifferentiated and upon phorbol 12‐myristate 13‐acetate (PMA)‐mediated differentiation of HL‐60 suspension cells, an acute promyelocytic leukemia subset cell line model from AML, into CD11b+/CD14− adherent macrophages.ResultsWe found that high NTS internalization correlated with increased matrix metalloproteinase‐9 expression, and basal macrophage cell migration. Whereas NTS dose‐dependently enhanced undifferentiated HL‐60 cells chemotaxis, it rather inhibited cell migration in differentiated macrophages through decreased Erk, MEK and Src signaling pathways. Epigallocatechin‐3‐gallate (EGCG), a diet‐derived polyphenol with anti‐inflammatory and chemopreventive properties, prevented PMA‐induced CD11b expression and NTS internalization.ConclusionsOur study evidences specific regulation and role for NTS receptors in HL‐60 differentiated macrophages, which could in part account for their contribution to immune evasion or tumor‐associated inflammation, and be prevented by the anti‐cancer property of diet‐derived polyphenols.Support or Funding InformationFunding: UQAM Foundation and Chaire in Cancer Prevention and TreatmentThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.