Autotaxin: a secreted autocrine/paracrine factor that promotes glioma invasion
Autotaxin: a secreted autocrine/paracrine factor that promotes glioma invasion
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DOI：
10.1007/s11060-007-9480-6
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发表时间：
2008-02-01
影响因子：
3.9
通讯作者：
Berens, Michael E.
中科院分区：
文献类型：
--
作者：
Hoelzinger, Dominique B.;Nakada, Mitsutoshi;Berens, Michael E.
多形性胶质母细胞瘤（GBM）是固有的侵袭性，它是从侵袭性细胞群，肿瘤复发。GBM侵袭转录组揭示了各种自分泌因子的过度表达，这些自分泌因子可以充当运动驱动因子，例如自分泌运动因子（ATX）。这些因子中的一些也可能具有旁分泌作用，调节肿瘤周围脑实质中细胞的行为。ATX产生溶血磷脂酸（LPA），其通过GBM以及星形胶质细胞、少突胶质细胞（ODC）和小胶质细胞表达的LPA受体发出信号;它们的活化表现出细胞特异性效应。ATX在体外和离体侵袭测定中刺激GBM细胞的侵袭。ATX活性增强表达LPA 1受体的细胞中的GBM粘附，以及刺激rac活化。GBM分泌的ATX也可具有旁分泌效应：ATX活性导致ODC粘附减少。ODC单层侵袭显示，表达ATX的U87和U251 GBM细胞通过ODC单层的侵袭显著多于ATX耗尽的细胞或表达失活ATX的细胞，表明分泌ATX的GBM细胞发现ODC比不表达ATX的细胞更少的屏障。驱动GBM侵袭的分泌因子可以具有自分泌和旁分泌作用;一种刺激GBM运动，另一种导致ODC脱粘。
Glioblastoma multiforme (GBM) is inherently invasive, and it is from the invasive cell population that the tumor recurs. The GBM invasion transcriptome reveals over-expression of various autocrine factors that could act as motility drivers, such as autotaxin (ATX). Some of these factors could also have paracrine roles, modulating the behavior of cells in the peri-tumoral brain parenchyma. ATX generates lysophosphatidic acid (LPA), which signals through LPA receptors expressed by GBM as well as in astrocytes, oligodendrocytes (ODC) and microglia; their activation manifest cell specific effects. ATX stimulates invasion of GBM cells in vitro and ex vivo invasion assays. ATX activity enhances GBM adhesion in cells expressing the LPA1 receptor, as well as stimulating rac activation. GBM secreted ATX can also have paracrine effects: ATX activity results in reduced ODC adhesion. ODC monolayer invasion showed that U87 and U251 GBM cells expressing ATX invaded through an ODC monolayer significantly more than cells depleted of ATX or cells expressing inactive ATX, suggesting that GBM cells secreting ATX find ODCs less of a barrier than cells that do not express ATX. Secreted factors that drive GBM invasion can have autocrine and paracrine roles; one stimulates GBM motility and the other results in ODC dis-adhesion.