Macrophage depletion decreases inflammation and tumorigenesis in the AOM/DSS mouse model of colon cancer

Macrophages have recently emerged as major players in the connection between inflammation and cancer; they represent up to 50% of the tumor mass and produce a wide array of inflammatory mediators with pro-tumoral functions. We used a macrophage depletion technique to examine the role of macrophages in colon cancer. To induce colon cancer, male C57BL/6 mice (n=20) received a single injection of AOM followed by three cycles of DSS supplemented water at concentrations of 2%, 1%, 1% at weeks 1, 4, and 7, respectively. Prior to the final DSS administration (week 7) and twice weekly thereafter for a duration of 5 weeks, mice (n=10/group) were administered 200μl of clodronate (CL 2 MDP) or PBS encapsulated liposomes via an intra-peritoneal route to deplete macrophages. Body weight, body composition, and symptom severity score were evaluated throughout the macrophage depletion period. Mice were sacrificed at 12 weeks following the initiation of colon cancer and colon tissue was analyzed for tumor burden, macrophage markers, and inflammatory mediators. There were no differences in body weight, body composition, or symptom severity score between the groups. Macrophage depletion decreased tumor number by ~25% and specifically medium tumor number by 50% (p