Secreted Protein Acidic and Rich in Cysteine (SPARC) promotes glioma migration and invasion, and does so, in part, by activating p38 mitogen activated protein kinase (P38 MAPK)–mitogen-activated protein kinase-activated protein kinase 2 (MK2)–heat shock protein 27 (HSP27) signaling. Phosphatase and tensin homolog (PTEN) suppresses SPARC-induced invasion, and decreases pAKT, serine (S)15- and S78HSP27. Therefore, SPARC function is affected by PTEN. Consequently, we propose targeting HSP27 in PTEN-wild-type gliomas, and both HSP27 and AKT in PTEN-null gliomas. Our in vitro studies support this therapeutic strategy; however, we do not know whether these pathways are reflected in human tumors. In this immunohistochemistry study, we examined SPARC, HSP27, and AKT expression and phosphorylation relative to tumor grade, to PTEN genetic status, to tumor invasion, and to patient survival. The results show that all glioma grades have elevated SPARC and S82HSP27. The expression of HSP27, S15HSP27, and S78HSP27, AKT and phospho (p)AKT increases with increasing grade. We found that the loss of PTEN correlates with increased HSP27, S15HSP27, S78HSP27 and pAKT. Finally, we observed that increasing levels of SPARC and pAKT correlate with shorter patient survival, as does any expression of S78HSP27. This study provides important rationale for targeting HSP27 alone, or HSP27 and AKT together, to treat glioma patients.
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