Elastase activity enhances the adhesion of neutrophil and cancer cells to vascular endothelial cells

被引:51
作者
Nozawa, F
Hirota, M
Okabe, A
Shibata, M
Iwamura, T
Haga, Y
Ogawa, M
机构
[1] Kumamoto Univ, Sch Med, Dept Surg 2, Kumamoto 8608556, Japan
[2] Miyazaki Med Coll, Dept Surg 1, Miyazaki 8891692, Japan
关键词
cancer; neutrophil elastase; elastase activity; adhesion; vascular endothelial cells; E-selectin;
D O I
10.1006/jsre.2000.6002
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. Elastase activity in cancer cells has been reported to promote their metastasis. Hence, we analyzed the influence of elastase activity of cancer cells on their responsive adhesion to vascular endothelial cells. Materials and methods. Human pancreatic (S2-007, S2-013, S2-020, S2-028) and colonic (COLO205) cancer cell lines were used. S2-007, S2-013, and S2-020 possess high elastase activity, whereas S2-028 and COLO205 have low elastase activity. Adhesive reactions of these cancer cells and neutrophils to TNF alpha -activated HUVEC were analyzed. Bound cells onto HUVEC were counted after incubation for 10 min. The effects of suppression of elastase activity by ZD8321, a potent elastase inhibitor, and supplementation of human neutrophil elastase (NE) on the adhesive reactions were also analyzed. In addition, E-selectin expression on HUVEC and concentrations of soluble E-selectin in the medium were measured. Results. Adhesion of cells with high intracellular elastase activity to TNF alpha -activated HUVEC was suppressed by ZD8321. On the other hand, adhesion of cells with low elastase activity was enhanced by exogenous NE. Expression of E-selectin, a key molecule in leukocyte-endothelial cell interaction, on HUVEC was increased by NE. Soluble E-selectin concentration in the medium increased after the adhesive reaction between neutrophils and HUVEC. This increase was thought to be due to the shedding of cell surface E-selectin. Such responses were inhibited by ZD8321. Conclusion. Elastase activity has a biological function of stimulating both the E-selectin expression on HUVEC and the resultant adhesive reaction of cancer cells with them. Inhibition of elastase activity is a potent strategy for controlling cancer metastasis. (C) 2000 Academic Press.
引用
收藏
页码:153 / 158
页数:6
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