Damtew B, Spagnuolo P J
Department of Medicine, Case Western Reserve University School of Medicine at MetroHealth Medical Center, Cleveland, Ohio 44109-1998, USA.
Prostaglandins Leukot Essent Fatty Acids. 1997 Apr;56(4):295-300. doi: 10.1016/s0952-3278(97)90573-1.
Adhesion of tumor cells (TC) to endothelial cells (EC) is necessary for movement of TC out of the interstitium to form metastatic deposits. This interaction may be influenced by proadhesive molecules such as lipoxygenase products of arachidonic acid metabolism. We studied the effect of inflammatory stimuli, A23187 calcium ionophore, n-formyl-methionyl-leucine-phenylalanine (FMLP) and phorbol myristate acetate (PMA) on TC-EC interaction. Adherence of metastatic breast tumor cell line (MCF-7), choriocarcinoma cell line (JEG-3), and non metastatic pituitary cell (GH-3) were assayed as the number of radiolabeled TC attached to EC (cpm/well). TC and EC were incubated with A23187, FMLP, and PMA for varying time periods. Lipoxygenase products (LTB4, 5-HETE) were measured under basal and stimulated conditions using RP-HPLC and RIA. There were no differences in basal adherence of TC lines to EC. When EC were incubated with stimuli, there were significant increases in the numbers of MCF-7 and JEG-3 cells adherent to EC compared to GH-3. Light and phase contrast microscopy confirmed that TC were attached to EC. Upon stimulation, GH-3 preferentially produced prostaglandins (PGI1(2)) while MCF-7 and JEG-3 produced lipoxygenase products (LTB4 and 5-HETE). Pre-incubation of MCF-7 and JEG-3 with the lipoxygenase inhibitor nordihydroguiaretic acid resulted in partial inhibition of adhesion to EC. Our data strongly indicate a role for lipoxygenase products of arachidonic acid in adherence of TC to EC.
肿瘤细胞（TC）与内皮细胞（EC）的黏附是TC离开间质形成转移灶所必需的。这种相互作用可能受促黏附分子如花生四烯酸代谢的脂氧合酶产物影响。我们研究了炎性刺激物、A23187钙离子载体、N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）和佛波酯肉豆蔻酸酯（PMA）对TC-EC相互作用的影响。通过测定附着于EC的放射性标记TC数量（每分钟计数/孔）来检测转移性乳腺癌细胞系（MCF-7）、绒毛膜癌细胞系（JEG-3）和非转移性垂体细胞（GH-3）的黏附情况。将TC和EC与A23187、FMLP和PMA孵育不同时间段。使用反相高效液相色谱法（RP-HPLC）和放射免疫分析法（RIA）在基础和刺激条件下测量脂氧合酶产物（白三烯B4、5-羟二十碳四烯酸）。各TC系与EC的基础黏附情况无差异。当EC与刺激物孵育时，与GH-3相比，黏附于EC的MCF-7和JEG-3细胞数量显著增加。光学显微镜和相差显微镜证实TC附着于EC。刺激后，GH-3优先产生前列腺素（前列环素I1(2)），而MCF-7和JEG-3产生脂氧合酶产物（白三烯B4和5-羟二十碳四烯酸）。用脂氧合酶抑制剂去甲二氢愈创木酸预孵育MCF-7和JEG-3可部分抑制其对EC的黏附。我们的数据有力地表明花生四烯酸的脂氧合酶产物在TC与EC的黏附中起作用。
