Since our previous studies demonstrated that the IGFBP-3/IGFBP-3R system suppresses tumor- and TNF-α-induced NF-κB activation and NF-κB-regulated genes including ICAM-1, VCAM-1, MCP-1 and IL-6 in a variety of cancers and inflammatory diseases [22,23,24,25,43,50], this indicates that colitis-induced activation neutrophils and subsequent activation of NSPs may lead to CAC through the increased production/activity of proinflammatory cytokines and decreased level of intact biologically-active IGFBP-3 in circulation and in colon tissue. Here, TNF is linked to cancer.