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Quantification of murine endothelial cell adhesion molecules in solid tumors
R R Langley1, J Russell, M J Eppihimer
1Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3932, USA.
The American Journal of Physiology
|September 14, 1999
Summary
Tumor vessels show higher selectin expression, potentially aiding leukocyte recruitment. However, tumor presence doesn't alter endothelial cell adhesion molecule (CAM) expression in other tissues.
Area of Science:
- Immunology
- Oncology
- Vascular Biology
Background:
- Effective anti-tumor immunity requires lymphocytes to infiltrate tumor stroma via adhesive interactions with endothelial cells.
- Reduced leukocyte-endothelial cell interactions in tumor microvessels are often attributed to decreased endothelial cell adhesion molecule (CAM) expression, but quantitative data is lacking.
Purpose of the Study:
- To quantitatively assess constitutive and tumor necrosis factor (TNF)-alpha-induced expression of key endothelial CAMs in various vascular beds of normal and tumor-bearing mice.
- To investigate the impact of solid tumors on endothelial CAM expression in both tumor and peripheral vasculature.
Main Methods:
- Utilized a dual-radiolabeled monoclonal antibody technique for precise quantification of endothelial CAMs.
- Measured 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).
- Compared expression levels in normal C57Bl/6 mice and RM-1 tumor-bearing mice across different vascular beds.
Main Results:
- Tumor vessels exhibited higher constitutive selectin expression compared to other vascular beds.
- Endothelial CAM expression in peripheral vascular beds remained unchanged in tumor-bearing mice, both constitutively and after TNF-alpha stimulation.
- Within tumors, TNF-alpha induced significant upregulation of P-selectin, ICAM-1, and VCAM-1, but E-selectin was refractory, and PECAM-1 and ICAM-2 were downregulated.
Conclusions:
- Solid tumors do not generally alter endothelial CAM expression in non-tumor vascular beds.
- Elevated constitutive selectin density in non-stimulated tumor vessels may facilitate the initial rolling of leukocytes into the tumor microenvironment.
- Differential regulation of CAMs within tumors suggests complex mechanisms governing immune cell trafficking.