| First Author | Li J | Year | 2017 |
| Journal | Mol Cancer Res | Volume | 15 |
| Issue | 4 | Pages | 467-477 |
| PubMed ID | 28108624 | Mgi Jnum | J:240407 |
| Mgi Id | MGI:5883364 | Doi | 10.1158/1541-7786.MCR-16-0309 |
| Citation | Li J, et al. (2017) Inflammatory Molecule, PSGL-1, Deficiency Activates Macrophages to Promote Colorectal Cancer Growth through NFkappaB Signaling. Mol Cancer Res 15(4):467-477 |
| abstractText | P-selectin glycoprotein ligand 1 (SELPLG/PSGL-1) is an inflammatory molecule that is functionally related to immune cell differentiation and leukocyte mobilization. However, the role of PSGL-1 in tumor development remains unknown. Therefore, this study investigates the mechanistic role of PSGL-1 in the development of intestinal tumors in colorectal cancer. ApcMin/+ mice are highly susceptible to spontaneous intestinal adenoma formation, and were crossbred with PSGL1-null mice to generate compound transgenic mice with a ApcMin/+;PSGL-1-/- genotype. The incidence and pathologic features of the intestinal tumors were compared between the ApcMin/+ mice and ApcMin/+;PSGL-1-/- mice. Importantly, PSGL-1-deficient mice showed increased susceptibility to develop intestinal tumors and accelerated tumor growth. Mechanistically, increased production of the mouse chemokine ligand 9 (CCL9/MIP-1gamma) was found in the PSGL-1-deficient mice, and the macrophages are likely the major source of macrophage inflammatory protein-1 gamma (MIP-1gamma). Studies in vitro demonstrated that macrophage-derived MIP-1gamma promoted colorectal cancer tumor cell growth through activating NFkappaB signaling. Conversely, restoration of the PSGL-1 signaling via bone marrow transplantation reduced MIP-1gamma production and attenuated the ability of ApcMin/+;PSGL-1-/- mice to generate intestinal tumors. In human colorectal cancer clinical specimens, the presence of PSGL-1-positive cells was associated with a favorable tumor-node-metastasis staging and decreased lymph node metastasis.Implications:PSGL-1 deficiency and inflammation render intestinal tissue more vulnerable to develop colorectal tumors through a MIP-1gamma/NFkappaB signaling axis. Mol Cancer Res; 15(4); 467-77. (c)2017 AACR. |
