Miranda ten Kate, Johannes Jeekel, Casper HJ van Eijck, Leo J Hofland, Peter M van Koetsveld
Objectives The potential role of surgeryinduced pro-inflammatory cytokines on the development of tumor recurrence in pancreatic cancer was investigated. Main outcome measures The adhesion of 3 human pancreatic carcinoma cell lines, PanC1, MiaPaCa and BxPC3 to monolayers of microvascular endothelial cells after preincubation with 0.1 or 10 ng/mL IL-1beta, TNF-alpha or IL-6 was assessed in a reproducible human in vitro assay. Untreated monolayers served as controls. Results Pre-incubation of microvascular endothelial cells with IL-1beta or TNF-alpha, but not IL-6, increased adhesion of all three tumor cell lines as compared to adhesion in the control group. Maximally stimulated adhesion for PanC1 reached 159%, for MiaPaCa 204% and for BxPC3 155% (all vs. the control, P0.001). Pre-incbation of microvascular endothelial cells with IL-1beta or TNF-alpha resulted in a significant upregulation of E-selectin, ICAM-1 and VCAM-1 expression. The addition of anti-Eselectin, anti-ICAM-1 or anti-VCAM-1 monoclonal antibodies did not decreaseadhesion to microvascular endothelial cells pre-incubated with IL-1beta. Therefore, enhanced tumor cell binding seems to be independent of these adhesion molecules. Conclusions Pro-inflammatory cytokines derived from surgical trauma may enhance tumor cell adhesion to microvascular endothelial cells and thus bring about more successful tumor cell implantation resulting in an increased risk of metastasis formation.
