Secretome signature of invasive glioblastoma multiforme.
Secretome signature of invasive glioblastoma multiforme.
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DOI：
10.1021/pr200210w
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发表时间：
2011-07-01
影响因子：
4.4
通讯作者：
Hathout, Yetrib
中科院分区：
文献类型：
--
作者：
Formolo, Catherine A.;Williams, Russell;Gordish-Dressman, Heather;MacDonald, Tobey J.;Lee, Norman H.;Hathout, Yetrib
关键词：
恶性胶质母细胞瘤的不可治愈性主要归因于它们的高度侵袭性以及对化疗和放疗的抗性。由于侵袭性部分由这些肿瘤分泌的蛋白决定，我们使用SILAC来表征四种胶质母细胞瘤细胞系（LN 18、T98、U118和U87）的分泌组。尽管U87和U118细胞都分泌高水平的众所周知的侵袭促进蛋白，但Matrigel侵袭测定显示U87细胞的侵袭性是U118细胞的8倍，这表明U87细胞分泌的其他蛋白可能有助于高度侵袭表型。事实上，我们鉴定了许多与侵袭性较小的细胞系相比由U87细胞高度或专门表达的蛋白质。其中最引人注目的包括ADAM 9、ADAM 10、组织蛋白酶B、组织蛋白酶L1、骨桥蛋白、神经纤毛蛋白-1、脑信号蛋白-7A、超盆和几丁质酶-3样蛋白1。U87细胞还表达显著低水平的一些细胞粘附蛋白，如骨膜蛋白和EMILIN-1。使用Pavlidis模板匹配的分泌组谱与相对侵袭性水平的相关性进一步表明这些蛋白在U87胶质母细胞瘤侵袭中的潜在作用。CH 3L 1的抗体抑制使U87细胞侵袭性降低30%。
The incurability of malignant glioblastomas is mainly attributed to their highly invasive nature coupled with resistance to chemo- and radiation therapy. Because invasiveness is partially dictated by the proteins these tumors secrete we used SILAC to characterize the secretomes of four glioblastoma cell lines (LN18, T98, U118 and U87). Although U87 and U118 cells both secreted high levels of well-known invasion promoting proteins, a Matrigel invasion assay showed U87 cells to be eight times more invasive than U118 cells, suggesting that additional proteins secreted by U87 cells may contribute to the highly invasive phenotype. Indeed, we identified a number of proteins highly or exclusively expressed by U87 cells as compared to the less invasive cell lines. The most striking of these include ADAM9, ADAM10, cathepsin B, cathepsin L1, osteopontin, neuropilin-1, semaphorin-7A, suprabasin and chitinase-3-like protein 1. U87 cells also expressed significantly low levels of some cell adhesion proteins such as periostin and EMILIN-1. Correlation of secretome profiles with relative levels of invasiveness using Pavlidis template matching further indicated potential roles for these proteins in U87 glioblastoma invasion. Antibody inhibition of CH3L1 reduced U87 cell invasiveness by 30%.
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