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Diminished Leukocyte-Endothelium Interaction in Tumor Microvessels¹

Department of Radiation Oncology [N. Z. W., M. W. D.] and Divisions of Plastic Surgery and Physiology [B. K.] and Cancer Center Biostatistics [R. D.], Duke University Medical Center, Durham, North Carolina 27710

Leukocyte-endothelium interaction in vivo consists of the rolling of leukocytes along the vascular wall and, under certain conditions, their adherence to endothelial cells. In a rat tumor microcirculation model (mammary adenocarcinoma implanted in rat skinfold window chamber), we demonstrated that this interaction, measured as flux of rolling leukocytes and density of adhering leukocytes, was significantly reduced in tumor microvessels compared to normal microvessels, both under control conditions and during inflammation induced by N-formylmethionylleucylphenylalanine (1 µM), bacterial lipopolysaccharide (1 µg/ml), or tumor necrosis factor (500 units/ml). We also measured the blood flow shear rate in the tumor and normal microvessels and found that the difference in shear rate between the two types of microvessels could not account for the differences in leukocyte-endothelium interaction. The diminished leukocyte-endothelium interaction in tumors under various stimulated conditions suggests that a number of adhesion molecules may not be expressed properly on tumor endothelial cells.

¹ This study was supported by Grant 5R01-CA40355 from the NIH.

² To whom requests for reprints should be addressed, at Box 3455, Duke University Medical Center, Durham, NC 27710.

Received 5/19/92. Accepted 6/15/92.

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