Rolling of human bone-metastatic prostate tumor cells on human bone marrow endothelium under shear flow is mediated by E-selectin
Rolling of human bone-metastatic prostate tumor cells on human bone marrow endothelium under shear flow is mediated by E-selectin
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DOI：
10.1158/0008-5472.can-04-0691
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发表时间：
2004-08-01
期刊：
影响因子：
11.2
通讯作者：
Kutok, JL
中科院分区：
文献类型：
--
作者：
Dimitroff, CJ;Lechpammer, M;Kutok, JL
与其他组织微血管的内皮衬里相比，前列腺肿瘤细胞优先粘附于骨髓内皮细胞（BMEC），这暗示了BMEC粘附在前列腺肿瘤骨转移倾向中的重要性。E（内皮）-sellectin，作为白细胞粘附到靶组织内皮细胞的启动子，在BMEC上组成型表达，表明前列腺肿瘤细胞可以使用这种粘附机制启动其迁移到骨中。在这份报告中，我们首次证明了人骨转移性前列腺肿瘤细胞在生理流动条件下在人BMEC上滚动。我们发现，这些动态粘附相互作用依赖于骨转移性前列腺肿瘤细胞上BMEC E-选择素和唾液酸化糖缀合物的表达。我们还建立了糖蛋白和鞘糖脂结构的重要性，显示唾液酸刘易斯X表位作为潜在的E-选择素配体骨转移性前列腺肿瘤细胞。唾液酸化糖蛋白和糖脂在骨转移性前列腺肿瘤细胞上的共表达触发了强有力的E-选择素结合活性，这与在人造血祖细胞上观察到的相同。通过蛋白质印迹分析，我们鉴定了候选的E-选择素糖蛋白配体;不同的带有唾液酸刘易斯X（或HECA-452抗原）的膜蛋白在M，130，000和M-r 220，000以及M-r 100，000至M-r 220，000范围内被分辨。HECA-452抗原在正常前列腺组织和低级别和高级别前列腺腺癌上表达的免疫组织化学分析显示，HECA-452抗原表达与前列腺肿瘤进展直接相关，并且可能指示获得E-选择素配体表达。这些发现为促进前列腺肿瘤细胞血行播散到骨中的潜在粘附机制提供了新的见解。
Prostate tumor cells preferentially adhere to bone marrow endothelial cells (BMECs) compared with endothelial linings from other tissue microvessels, implicating the importance of BMEC adhesion in the predilection of prostate tumor metastasis to bone. E (endothelial)-sellectin, which functions as an initiator of leukocyte adhesion to target tissue endothelium, is constitutively expressed on BMECs, suggesting that prostate tumor cells could use this adhesive mechanism to initiate their migration into bone. In this report, we demonstrate for the first time that human bone-metastatic prostate tumor cells roll on human BMECs under physiological flow conditions. We show that these dynamic adhesive interactions are dependent on the expression of BMEC E-selectin and sialylated glycoconjugates on bone-metastatic prostate tumor cells. We also establish the importance of both glycoprotein(s) and glycosphingolipid structures displaying sialyl Lewis X epitopes as potential E-selectin ligands on bone-metastatic prostate tumor cells. Coexpression of sialylated glycoproteins and glycolipids on bone-metastatic prostate tumor cells triggers robust E-selectin binding activity, which is identical to that observed on human hematopoietic progenitor cells. By Western blot analysis, we identify candidate E-selectin glycoprotein ligand(s); distinct sialyl Lewis X (or HECA-452 antigen)-bearing membrane proteins were resolved at M, 130,000 and M-r 220,000 as well as others ranging from M-r 100,000 to M-r 220,000. Immunohistochemical analysis of HECA-452 antigen expression on normal prostate tissue and on low- and high-grade prostate adenocarcinoma shows that HECA-452 antigen expression is directly associated with prostate tumor progression and may indicate acquisition of E-selectin ligand expression. These findings provide novel insight into potential adhesive mechanisms promoting hematogenous dissemination of prostate tumor cells into bone.