Involvement of integrin alpha(v)beta(3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells.

Involvement of integrin alpha(v)beta(3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells.
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整合素α(v)β(3)和细胞粘附分子L1参与黑色素瘤细胞的跨内皮迁移。

DOI:
10.1091/mbc.12.9.2699
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发表时间:
2001
影响因子:
3.3
通讯作者:
Siu,CH
Siu,CH
中科院分区:
生物学3区
文献类型:
--
作者:
Voura,EB;Ramjeesingh,RA;Montgomery,AM;Siu,CH

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肿瘤转移涉及许多阶段特异性粘附相互作用。几种细胞粘附分子,特别是整合素αvβ3的表达与肿瘤细胞的转移潜能相关。在这项研究中,我们使用了一种新的体外试验来研究αvβ 3在黑色素瘤细胞通过单层人肺微血管内皮细胞迁移中的作用。共聚焦显微镜显示黑色素瘤膜突起和伪足上存在整合素αvβ 3,穿透内皮连接。αvβ 3在内皮细胞和黑色素瘤细胞之间的异型接触中也富集。环精氨酸-甘氨酸-天冬氨酸肽或抗αvβ 3单克隆抗体LM 609均可抑制黑色素瘤细胞的跨内皮迁移。虽然血小板内皮细胞粘附分子-1和L1都与整合素αvβ3结合,但在黑色素瘤跨内皮迁移过程中,只有L1作为αvβ 3的潜在配体。此外,抗L1的多克隆抗体部分抑制黑色素瘤细胞的跨内皮迁移。然而,加入L1和αvβ 3抗体没有显示出累加效应,表明它们是同一粘附系统的组分。总之,这些数据表明黑色素瘤细胞上的整合素αvβ 3和内皮细胞上的L1之间的相互作用在黑色素瘤细胞的跨内皮迁移中起重要作用。
Tumor metastasis involves many stage-specific adhesive interactions. The expression of several cell adhesion molecules, notably the integrin αvβ3, has been associated with the metastatic potential of tumor cells. In this study, we used a novel in vitro assay to examine the role of αvβ3in the transmigration of melanoma cells through a monolayer of human lung microvascular endothelial cells. Confocal microscopy revealed the presence of the integrin αvβ3on melanoma membrane protrusions and pseudopods penetrating the endothelial junction. αvβ3was also enriched in heterotypic contacts between endothelial cells and melanoma cells. Transendothelial migration of melanoma cells was inhibited by either a cyclic Arg-Gly-Asp peptide or the anti-αvβ3monoclonal antibody LM609. Although both platelet endothelial cell adhesion molecule-1 and L1 are known to bind integrin αvβ3, only L1 serves as a potential ligand for αvβ3during melanoma transendothelial migration. Also, polyclonal antibodies against L1 partially inhibited the transendothelial migration of melanoma cells. However, addition of both L1 and αvβ3antibodies did not show additive effects, suggesting that they are components of the same adhesion system. Together, the data suggest that interactions between the integrin αvβ3on melanoma cells and L1 on endothelial cells play an important role in the transendothelial migration of melanoma cells.
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