Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor

Objective: To investigate the effect of different cytokines that are presen t in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cel l transmigration. Design: Laboratory study. Setting: University hospital, ireland. Material: Isolated human PMN and cultured human breast tumour cell line, MD A-MB-231. Interventions: Human PMN treated with either tumour-conditioned medium or d ifferent media neutralised with monoclonal antibodies (MoAb), and MDB-MB-23 1 cells were plated on macrovascular and microvascular endothelial monolaye rs in collagen-coated transwells to assess migration of tumour cells. Main Outcome Measures: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. Results: tumour-conditioned medium contained high concentrations of granulo cyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial gr owth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-st imulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb signifi cantly reduced PMN-induced transmigration of tumour cells treated with tumo ur-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VE GF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p,< 0.05). Conclusion. These results indicate that the GM-CSF that is present in tumou r-conditioned medium may be involved, at least in part, in alterations in P MN function mediated by the medium and subsequently PMN-induced transmigrat ion of tumour cells.