Human neutrophils facilitate tumor cell transendothelial migration.
AffiliationDepartment of Surgery, Cork University Hospital, University College Cork, Wilton,, Cork, Ireland.
Cell Movement/drug effects/*physiology
Culture Media, Conditioned/pharmacology
Intercellular Adhesion Molecule-1/immunology/metabolism
Tumor Cells, Cultured/cytology
MetadataShow full item record
CitationAm J Physiol Cell Physiol. 2001 Apr;280(4):C814-22.
JournalAmerican journal of physiology. Cell physiology
AbstractTumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.
- Distinct role of hydrodynamic shear in leukocyte-facilitated tumor cell extravasation.
- Authors: Slattery MJ, Liang S, Dong C
- Issue date: 2005 Apr
- Expression and polarization of intercellular adhesion molecule-1 on human intestinal epithelia: consequences for CD11b/CD18-mediated interactions with neutrophils.
- Authors: Parkos CA, Colgan SP, Diamond MS, Nusrat A, Liang TW, Springer TA, Madara JL
- Issue date: 1996 Jul
- Dopamine attenuates the chemoattractant effect of interleukin-8: a novel role in the systemic inflammatory response syndrome.
- Authors: Sookhai S, Wang JH, Winter D, Power C, Kirwan W, Redmond HP
- Issue date: 2000 Sep
- Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1.
- Authors: Luscinskas FW, Cybulsky MI, Kiely JM, Peckins CS, Davis VM, Gimbrone MA Jr
- Issue date: 1991 Mar 1
- Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.
- Authors: Wu QD, Wang JH, Bouchier-Hayes D, Redmond HP
- Issue date: 2000 May