Effect of IL-6 on tumor cell invasion of vascular endothelial monolayers.
The effect of interleukin-6 (IL-6) on the invasive capacity of B16-F1 mouse melanoma cells into vascular endothelial monolayers was examined, and an in vitro assay system for the quantitative determination of tumor cell invasiveness, using confocal microscopy with a fluorescence image analyzer, was developed. First, the invasive capacity of B16-F1 mouse melanoma cells against bovine vascular endothelial monolayers was estimated; then, the gap junctional intercellular communication (GJIC) of endothelial cells was examined. Treatment of endothelial cells with IL-6 resulted in a remarkable increase in the invasion of tumor cells into the endothelial monolayer, which was found to be significant from 25 ng/ ml, and peaked at levels of more than 50 ng/ml. This stimulatory effect of IL-6, which was observed from 3 h after the initiation of treatment and lasted for up to 24 h, was abolished by the addition of the anti-IL-6 antibody. Although phase-contrast microscopy did not reveal any morphological changes in the endothelial cells following treatment with 25-200 ng/ml IL-6 for 24 h, the GJIC was observed to be significantly decreased. These findings indicate that the invasive capacity of tumor cells into endothelial cells is affected by IL-6.
Kitamura
Y
Y
Department of Physiological Chemistry, School of Dentistry, Tokyo Medical and Dental University, Japan.
Morita
I
I
Nihei
Z
Z
Mishima
Y
Y
Murota
S
S
D000704:Analysis of Variance; D000818:Animals; D002417:Cattle; D002450:Cell Communication / Q000502:physiology; D003470:Culture Media; D004730:Endothelium, Vascular / Q000473:pathology*; D017629:Gap Junctions / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology*; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured
D003470:Culture Media; D015850:Interleukin-6