Large amounts of tumor-associated macrophages (TAM), which are predominately localized in
hypoxia area of the
tumor tissue, are associated with the malignant progression of the
tumor. In the present study, we investigated the inhibitory effects of modified
citrus pectin (MCP), a natural dietary
polysaccharide, on the survival and polarization of TAM in relation to its inhibition on the growth and migration of
breast cancer. M2 macrophages polarized from human monocyte THP-1 were chosen as a model for TAM. We showed that MCP (0.06%-1%) concentration-dependently suppressed the survival of TAM through inhibiting
glucose uptake with a greater extent in
hypoxia than in normoxia. Furthermore, MCP treatment decreased ROS level in TAM through its reducibility and inhibiting
galectin-3 expression, leading to inhibition of
glucose transporter-1 expression and
glucose uptake. In addition, MCP suppressed M2-like polarization via inhibiting STAT3 phosphorylation. Moreover, the
tumor-promoting effect of TAM could be restrained by MCP treatment as shown in human
breast cancer MDA-MB-231 cells in vitro and in mouse
breast cancer 4T1-luc orthotopic and
metastasis models. In both
tumor tissue and lung tissue of the mouse
tumor models, the number of TAM was significantly decreased after MCP treatment. Taken together, MCP may be a promising agent for targeting TAM in
tumor hypoxic microenvironment for
breast cancer treatment.