HMGB1 Attenuates Anti-Metastatic Defense of the Lymph Nodes in Colorectal Cancer

Background: Cancer-secreted high mobility group 1 (HMGB1) induces apoptosis of macrophages and suppresses the host anti-cancer immune system. Objective: We here examined the effect of HMGB1 on macrophages in the lymph nodes of colorectal cancer (CRC) patients. Methods: Regional lymph nodes of 50 Dukes C CRCs were compared with 50 Dukes B CRCs. Results: Dukes C tumors exhibited higher HMGB1 labeling indices and higher HMGB1 concentrations in primary tumors than Dukes B CRCs. Macrophages in the regional lymph nodes were decreased in non-metastasized nodes as well as metastasized nodes in Dukes C cases, whereas macrophage numbers in Dukes B nodes were higher than in Dukes C nodes. Nodal HMGB1 concentration was higher in Dukes C nodes than in Dukes B nodes, being inversely correlated with macrophage numbers. Nodal HMGB1 concentration was correlated with HMGB1 concentration and lymph vessel density in the primary tumors. Conclusion: These data suggest that HMGB1 secreted from primary tumors spread to the regional lymph nodes decreases the number of macrophages to attenuate the anti-metastatic defense of the lymph nodes in patients with CRCs. Copyright (C) 2010 S. Karger AG, Basel