Influence of hypoxia and tumour-conditioned medium on endothelial cell adhesion molecule expression in vitro.
BACKGROUND
Cell adhesion molecule expression by tumour endothelium is involved in the efficacy of several cancer therapies. This study investigated the effect of tumour microenvironmental conditions, i.e. reduced oxygenation and tumour-conditioned medium (TCM), on the expression of adhesion molecules by HUVECs.


METHODS
E-selectin (CD62-E), VCAM-1 (CD106) and PECAM-1 (CD31) were measured using an ELISA assay. Reduced oxygen tension (approximately 0%, 1% vs. 20%) and the presence of TCM from human breast adenocarcinoma MDA-MB-231 was investigated following the treatment of HUVECs with TNFalpha.


RESULTS
E-selectin (peak at 4 hours) and VCAM-1 (peak at 24 hours) expression were significantly increased by TNFalpha but unchanged by reduced oxygenation. TCM significantly attenuated E-selectin (71%), VCAM-1 (74%) and PECAM (62%) response to TNFalpha.


CONCLUSIONS
Tumour-secreted factors have a greater inhibitory action than reduced oxygen tension on HUVECs adhesion molecule expression induced by TNFalpha. Reduced expression of adhesion molecules may limit cancer therapies that mediate their action by host cell infiltration.
Watts
Margaret E
ME
Tumour Microcirculation Group, Gray Cancer Institute, Northwood, UK.
Parkins
Charles S
CS
Chaplin
David J
DJ
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D017077:Culture Media, Conditioned; D019040:E-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D010100:Oxygen