Maresin 1: a Novel Macrophage Derived Endogenous Proresolving Inhibitor of Primary Tumor Growth and Metastasis

Abstract

BackgroundChemotherapy and radiation reduce tumor burden by killing tumor cells, but as a consequence, create tumor cell debris. The debris of dead cancer cells acts as a source of tumor‐stimulation, via inflammation, on the few surviving cells contributing to tumor relapse. Thus chemotherapy may be a doubled‐edged sword. Maresin 1 (MaR1), a key mediator of inflammation resolution, is biosynthesized by human macrophages from endogenous docosahexaenoic acid. We hypothesize that maresins represent a novel modality in cancer treatment by inhibiting tumor growth and metastasis by enhancing endogenous clearance of tumor debris by macrophage phagocytosis.ResultsFlow cytometry confirmed chemotherapy and targeted therapy (tamoxifen)‐induced apoptotic tumor cell debris. MaR1 stimulated macrophage phagocytosis of chemotherapy‐induced cell debris (e.g. breast carcinoma and melanoma) by 123% to 206%. Systemic administration of MaR1 inhibits primary tumor growth by promoting the resolution of inflammation without toxicity. ConclusionsWe demonstrate for the first time that maresins inhibit primary tumor growth and metastasis via the stimulation of macrophage phagocytosis of chemotherapy‐induced tumor cell debris. Thus, the MaR1 pathway or the enhancement of endogenous resolution processes, offers an entirely novel approach for clearing tumor cells debris induced by conventional cancer therapy.