Quantification of murine endothelial cell adhesion molecules in solid tumors.
Coordinated adhesive interactions between lymphocyte receptors and endothelial cell adhesion molecules (CAMs) are a prerequisite for effector cell entry into tumor stroma. Whereas the diminished leukocyte-endothelial cell interactions observed in tumor microvessels have been attributed to a reduced expression of endothelial CAMs, there is no quantitative data bearing on this issue. The dual-radiolabeled monoclonal antibody technique was used to quantify constitutive and tumor necrosis factor (TNF)-alpha-induced expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), ICAM-2, P-selectin, E-selectin, and platelet-endothelial cell adhesion molecule 1 (PECAM-1) in different vascular beds of normal (C57Bl/6) and RM-1 tumor-bearing mice. When corrected for endothelial surface area, the constitutive expression of selectins in tumor vessels was higher than that observed in other vascular beds. Both constitutive and induced expression of endothelial CAMs in peripheral vascular beds did not differ between normal and tumor-bearing mice. Within the tumor, the magnitude of the upregulation of P-selectin, ICAM-1, and VCAM-1 after TNF-alpha was similar to that within other vascular beds. E-selectin expression in tumors was refractory to TNF-alpha, whereas PECAM-1 and ICAM-2 expression were significantly reduced. Our findings suggest that the presence of a solid tumor does not influence endothelial CAM expression in other vascular beds and that the higher density of selectins in nonstimulated tumor vessels may promote the recruitment of rolling leukocytes in this tissue.
Langley
R R
RR
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3932, USA.
Russell
J
J
Eppihimer
M J
MJ
Alexander
S J
SJ
Gerritsen
M
M
Specian
R D
RD
Granger
D N
DN
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha