ICAM-1 Mediated Tumor-Mesothelial Cell Adhesion is Modulated by IL-6 and TNF-α: A Potential Mechanism by Which Surgical Trauma Increases Peritoneal Metastases

摘要

Peritoneal metastases frequently occur in different gastrointestinal cancers and have a poor prognosis. It is known that surgical injury promotes tumor growth and local recurrence rates and also the degree of surgical trauma correlated with the amount of tumor implantation into the peritoneum. The mechanism that mediates tumor cell adhesion to the mesothelium is not fully understood. This study investigates the role of ICAM-1, an important mediator of trans-mesothelial leucocyte migration, in tumor-mesothelial interactions as the initial step in the development of peritoneal recurrence using an in vitro model incorporating mesothelial cell monolayer derived from omental samples. We also investigate how the cytokines interleukins 6 (IL-6) and tumor necrosis factor alpha (TNF-α) modulate this process. We demonstrate that ICAM-1 blockade reduces the ability of both pancreatic and colonic cancer cell lines to adhere to the mesothelium. Preincubation of the mesothelial cell monolayer with either IL-6 or TNF-α enhances tumor cell adhesion, and this is associated with an increased expression of ICAM-1. Mesothelial CD44 expression, which has previously been implicated in this process, was unaffected by these cytokines. The use of an inhibitory monoclonal antibody against ICAM-1 attenuated the enhanced adhesion mediated by IL-6 or TNF-α. This study suggests that mesothelial ICAM-1 plays a role in the adhesion of tumor cells to the peritoneum in the development of peritoneal metastases.