Pro-inflammatory cytokines affect pancreatic carcinoma cell. Endothelial cell interactions.
OBJECTIVE
The potential role of surgery-induced pro-inflammatory cytokines on the development of tumor recurrence in pancreatic cancer was investigated.


METHODS
The adhesion of 3 human pancreatic carcinoma cell lines, PanC1, MiaPaCa and BxPC3 to monolayers of microvascular endothelial cells after pre-incubation 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, P<0.001). Pre-incubation of microvascular endothelial cells with IL-1beta or TNF-alpha resulted in a significant up-regulation of E-selectin, ICAM-1 and VCAM-1 expression. The addition of anti-E-selectin, anti-ICAM-1 or anti-VCAM-1 monoclonal antibodies did not decrease adhesion 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.
ten Kate
Miranda
M
Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands.
Hofland
Leo J
LJ
van Koetsveld
Peter M
PM
Jeekel
Johannes
J
van Eijck
Casper H J
CH
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology* / Q000494:pharmacology; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000592:standards; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology; D009364:Neoplasm Recurrence, Local / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D015203:Reproducibility of Results; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016207:Cytokines; D019040:E-Selectin; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1