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 present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration.


METHODS
Laboratory study.


METHODS
University hospital, Ireland.


METHODS
Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231.


METHODS
Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells.


METHODS
Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration.


RESULTS
tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-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-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05).


CONCLUSIONS
These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.
Wu
Q D
QD
Department of Surgery, Cork University Hospital, University College Cork, Ireland.
Wang
J H
JH
Bouchier-Hayes
D
D
Redmond
H P
HP
D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology; D015815:Cell Adhesion Molecules; D002465:Cell Movement; D003470:Culture Media; D016207:Cytokines / Q000502:physiology; D004730:Endothelium, Vascular; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000502:physiology*
D015815:Cell Adhesion Molecules; D003470:Culture Media; D016207:Cytokines; D007377:Interleukin-3; D016209:Interleukin-8; D016178:Granulocyte-Macrophage Colony-Stimulating Factor