Inflammatory Molecule, PSGL-1 , Deficiency Activates Macrophages to Promote Colorectal Cancer Growth through NFκB Signaling

P-selectin glycoprotein ligand 1 (SELPLG/ ) is an inflammatory molecule that is functionally related to immune cell differentiation and leukocyte mobilization. However, the role of in tumor development remains unknown. Therefore, this study investigates the mechanistic role of in the development of intestinal tumors in colorectal cancer. Apc mice are highly susceptible to spontaneous intestinal adenoma formation, and were crossbred with PSGL1-null mice to generate compound transgenic mice with a Apc ; genotype. The incidence and pathologic features of the intestinal tumors were compared between the Apc mice and Apc ; mice. Importantly, -deficient mice showed increased susceptibility to develop intestinal tumors and accelerated tumor growth. Mechanistically, increased production of the mouse chemokine ligand 9 (CCL9/MIP-1γ) was found in the -deficient mice, and the macrophages are likely the major source of macrophage inflammatory protein-1 gamma (MIP-1γ). Studies demonstrated that macrophage-derived MIP-1γ promoted colorectal cancer tumor cell growth through activating NFκB signaling. Conversely, restoration of the signaling via bone marrow transplantation reduced MIP-1γ production and attenuated the ability of Apc ; mice to generate intestinal tumors. In human colorectal cancer clinical specimens, the presence of -positive cells was associated with a favorable tumor-node-metastasis staging and decreased lymph node metastasis. deficiency and inflammation render intestinal tissue more vulnerable to develop colorectal tumors through a MIP-1γ/NFκB signaling axis. .