Effects of Intratumoral Injection of CCL2 on Monocyte–Endothelial Cell Interactions in Mouse Pancreatic Cancer

ABSTRACT Objective: Although monocyte infiltration is an important aspect of the host response to tumor growth, the mechanisms of recruitment and their impact on tumor growth are still unknown. The authors studied monocyte–endothelial interaction and the effect of chemokine CCL2 in orthotopic mouse pancreatic cancer. Methods: The rolling and adhesion of labeled monocytes in peritumoral and intratumoral areas were assessed by using an intravital microscope. Further, the effects of intratumoral injection or superfusion of CCL2 on in situ recruitment of monocytes and other immune cells and adhesion molecules were investigated. Results: More monocytes were recruited in the peritumoral area than in the intratumoral area with increased vascular interaction, and the effect was more apparent by intratumoral CCL2 injection than superfusion. In both CCL2-treated groups infiltration of CD11b+, CD68+, and CD4+ cells were increased, but the magnitude of increase was larger in intratumoral injection. Quantitative RT-PCR for the tumor tissue revealed that ICAM-1 expression was increased by the injection of CCL2. Conclusion: These results show intratumoral injection of CCL2 induces effective interaction between monocytes and endothelial cells in the peritumoral area of pancreatic cancer accompanied by the upregulation of ICAM-1 and may possibly become a tool for immunotherapy by promoting the infiltration of immune cells in cancers.