Invasion-associated MMP-2 and MMP-9 are Up-regulated Intracellularly in Concert with Apoptosis Linked to Melanoma Cell Detachment
Invasion-associated MMP-2 and MMP-9 are Up-regulated Intracellularly in Concert with Apoptosis Linked to Melanoma Cell Detachment
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DOI：
10.1007/s10585-005-8672-8
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发表时间：
2005
影响因子：
4
通讯作者：
A. Pereira;M. Strasberg-Rieber;M. Rieber
中科院分区：
文献类型：
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作者：
A. Pereira;M. Strasberg-Rieber;M. Rieber
基质金属蛋白酶，如 MMP-2 和 MMP-9 明胶酶，显示出作为细胞外/细胞表面酶的多种功能，并因其基质降解能力和参与细胞运动而被广泛认可。鉴于贴壁细胞在迁移过程中的附着减少，并且在凋亡过程中也从其基质分离，我们现在研究细胞外基质结合的明胶酶以及细胞内 MMP-2 和 MMP-9 是否随着死亡诱导刺激的进展而被修饰。该报告显示，黑色素瘤细胞因 2-乙酰基呋喃萘醌 (FNQ) 的反应而死亡，这通过膜联蛋白 V 结合增强、pro-MMP-2 胞质表达增加以及颗粒 MMP-9 的细胞内激活来证明。这些变化与底物附着的 40 kDa 明胶酶的早期激活相关，与细胞外基质结合的激活 MMP-2 的变化相反。随后分泌的 MMP-9 的激活和细胞凋亡相关的聚 ADP-核糖聚合酶 (PARP) 片段的诱导与细胞脱离相关。我们的数据表明，细胞内激活的明胶酶可能会裂解除明胶之外的与存活相关的底物，这些底物共享 Gly-Leu/Iso-Pro，如胶原蛋白结合乙酰胆碱酯酶，从而将它们与细胞脱离相关的细胞凋亡联系起来。
Matrix metalloproteinases, like MMP-2 and MMP-9 gelatinases, show multiple functions as extracellular/cell-surface enzymes, and are broadly recognised for their matrix-degrading ability and involvement in cell motility. Given that adherent cells have reduced attachment during migration and also detach from their substratum during apoptosis, we now investigated whether extracellular matrix-bound gelatinases and intracellular MMP-2 and MMP-9 are modified with progression of death-inducing stimuli. This report shows that melanoma cells undergoing death in response to 2-acetyl furanonaphtoquinone (FNQ) as evidenced by greater Annexin V binding, increased cytosolic expression of pro-MMP-2 and intracellular activation of particulate MMP-9. These changes were associated with early activation of a substrate-attached 40 kDa gelatinase reciprocal with changes in extracellular matrix-bound activated MMP-2. A subsequent activation of secreted MMP-9 and induction of apoptosis-associated fragmentation of poly ADP-Ribose polymerase (PARP) correlated with cell detachment. Our data suggests that intracellularly activated gelatinases may cleave survival-associated substrates other than gelatin that share the Gly-Leu/Iso-Pro like collagen-binding acetylcholinesterase, thereby linking them to apoptosis associated with cell detachment.