Microglial stress inducible protein 1 promotes proliferation and migration in human glioblastoma cells. Neuroscience

Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21949-590 Rio de Janeiro, Brazil.
Neuroscience (Impact Factor: 3.36). 10/2011; 200:130-41. DOI: 10.1016/j.neuroscience.2011.10.025
Source: PubMed


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 (PrP(C)) 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 STI1 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-PrP(C) neutralizing antibody. Moreover, rec STI1 and rec STI1(Δ230-245), which lack the PrP(C) 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 STI1 is secreted by microglia and favors tumor growth and invasion through the participation of MMP-9 in a PrP(C)-independent manner.


Available from: Anna Carolina Carvalho da Fonseca
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    • "It is currently accepted that GBMs can also be derived from tumor stem cells. As said before, GBMs are heterogeneous, due to the presence of non-tumor cells such as astrocytes, microglial cells and endothelial cells (Fonseca et al., 2012; Kahn et al., 2012; Lima et al., 2012). Endogenous, non-tumoral, neural stem cells are able to migrate from the subventricular zone (SVZ) toward glial brain tumors, damaged or regenerating tissue, and inflammation sites (Aboody et al., 2000; Tang et al., 2003; Synowitz et al., 2006; Walzlein et al., 2008; Díaz-Coránguez et al., 2013). "
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    Frontiers in Cellular Neuroscience 12/2014; 8(418):1-13. DOI:10.3389/fncel.2014.00418 · 4.29 Impact Factor
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    • "Another GAM-associated mechanism, the CX3CR1/CX3CL1 interaction, can also induce MMPs production resulting in glioma invasion [64]. A recently described factor, STI1 (cochaperone stress inducible factor 1) secreted by microglia was shown to favor tumor growth and invasion through the participation of MMP-9 [65]. Thus, glioma cells stimulate microglia to increase the breakdown of extracellular matrix, thereby, promoting glioma invasion. "
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    Clinical and Developmental Immunology 07/2013; 2013(4):285246. DOI:10.1155/2013/285246 · 2.93 Impact Factor
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    • "Recently, it was demonstrated that the cochaperone stress inducible protein-1 (STI1), a cellular prion protein (PrPc) ligand, released by primary microglia cells promotes proliferation and migration of glioma cell lines in a PrPc-independent fashion (possibly involving MMP-9). Moreover, this proliferative effect was specific to brain macrophages, since conditioned medium from peritoneal macrophages was unable to induce glioma cells growth [33]. As previously discussed, glioma and microglia interactions mediated through EGF and CSF-1 can also increase tumor invasion [10]. "
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    Clinical and Developmental Immunology 06/2013; 2013(4):264124. DOI:10.1155/2013/264124 · 2.93 Impact Factor
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