MICROGLIAL STRESS INDUCIBLE PROTEIN 1 PROMOTES PROLIFERATION AND MIGRATION IN HUMAN GLIOBLASTOMA CELLS
MICROGLIAL STRESS INDUCIBLE PROTEIN 1 PROMOTES PROLIFERATION AND MIGRATION IN HUMAN GLIOBLASTOMA CELLS
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DOI：
10.1016/j.neuroscience.2011.10.025
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发表时间：
2012-01-03
期刊：
影响因子：
3.3
通讯作者：
Lima, F. R. S.
中科院分区：
文献类型：
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作者：
da Fonseca, A. C. C.;Romao, L.;Lima, F. R. S.
小胶质细胞活化是肿瘤进展和浸润的关键事件。我们以前已经证明，共伴侣应激诱导蛋白1（STI 1），细胞朊蛋白（PrPc）配体，促进胶质母细胞瘤（GBM）增殖。在本研究中，我们研究了小胶质细胞STI 1在人胶质母细胞瘤细胞系GBM 95的生长和侵袭中的影响。我们证明了小胶质细胞分泌到培养基中的可溶性因子（小胶质细胞条件培养基; MG CM）引起GBM 95细胞增殖的两倍增加。当从MG CM中取出Sill时，这种效应逆转。在这种情况下，我们已经表明，小胶质细胞合成和分泌STI 1。有趣的是，当GBM细胞维持在MG CM或含有抗PrPc中和抗体的MG CM中时，未观察到增殖率的差异。此外，缺乏PrPc结合位点的rec STI 1和rec STI 1（Delta 230-245）均促进相似水平的GBM 95增殖。在迁移实验中，MG CM有利于GBM 95细胞的迁移，但当从MG CM中去除STI 1时，迁移失败。我们检测了MG CM中的金属蛋白酶9（MMP-9）活性，当用抗STI 1抗体处理培养的小胶质细胞时，MMP-9活性降低。我们的研究结果表明，Sill是由小胶质细胞分泌，有利于肿瘤的生长和侵袭，通过参与MMP-9在一个PrPc的独立方式。(C)2011年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Microglial activation is a key event in the progression and infiltration of tumors. We have previously demonstrated that the co-chaperone stress inducible protein 1 (STI1), a cellular prion protein (PrPc) ligand, promotes glioblastoma (GBM) proliferation. In the present study, we examined the influence of microglial STI1 in the growth and invasion of the human glioblastoma cell line GBM95. We demonstrated that soluble factors secreted by microglia into the culture medium (microglia conditioned medium; MG CM) caused a two-fold increase in the proliferation of GBM95 cells. This effect was reversed when Sill was removed from the MG CM. In this context, we have shown that microglial cells synthesize and secrete STI1. Interestingly, no difference was observed in proliferation rates when GBM cells were maintained in MG CM or MG CM containing an anti-PrPc neutralizing antibody. Moreover, rec STI1 and rec STI1(Delta 230-245), which lack the PrPc binding site, both promoted similar levels of GBM95 proliferation. In the migration assays, MG CM favored the migration of GBM95 cells, but migration failed when STI1 was removed from the MG CM. We detected metalloproteinase 9 (MMP-9) activity in the MG CM, and when cultured microglia were treated with an anti-STI1 antibody, MMP-9 activity decreased. Our results suggest that Sill is secreted by microglia and favors tumor growth and invasion through the participation of MMP-9 in a PrPc-independent manner. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.