Targeting of crosstalk between tumor and tumor microenvironment by ?-D mannuronic acid (M2000) in murine breast cancer model

Abstract

Metastasis is the main cause of death in breast cancer patients. Inflammatory processes following crosstalk between tumor cells and tumor microenvironment play an important role in progression and metastasis of cancer. Hence, targeting of these interactions may represent a novel promising strategy for breast cancer therapy. So, we investigated the effects of ?-D mannuronic acid (BDM), a new antiinflammatory agent, on 4T1 breast cancer cell line both in vitro and in vivo. Proliferation assays revealed low-cytotoxic effect of BDM on 4T1 cells. However, BDM reduced activity of MMP-2, MMP-9 and significantly decreased the adhesion of 4T1 cells to extracellular matrix (ECM) in a dose-dependent manner. The in vivo results demonstrated that BDM strongly inhibits tumor growth and increases lifespan as compared with control mice. The decrease in tumor mass was associated with decreased metastasis, recruitment, and frequency of inflammatory cells in tumor tissue. Our preclinical findings demonstrated that BDM therapy not only prevents formation of chronic inflammatory response but also inhibits crosstalk between tumor cells and their microenvironment, which is associated with reduction of tumor growth and metastasis arrest. Our data imply the use of BDM therapy in future clinical trials to open a new horizon for breast cancer therapy. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.