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Periostin is a novel therapeutic target that predicts and regulates glioma malignancy.

ABSTRACT: Periostin is a secreted matricellular protein critical for epithelial-mesenchymal transition and carcinoma metastasis. In glioblastoma, it is highly upregulated compared with normal brain, and existing reports indicate potential prognostic and functional importance in glioma. However, the clinical implications of periostin expression and function related to its therapeutic potential have not been fully explored.Periostin expression levels and patterns were examined in human glioma cells and tissues by quantitative real-time PCR and immunohistochemistry and correlated with glioma grade, type, recurrence, and survival. Functional assays determined the impact of altering periostin expression and function on cell invasion, migration, adhesion, and glioma stem cell activity and tumorigenicity. The prognostic and functional relevance of periostin and its associated genes were analyzed using the TCGA and REMBRANDT databases and paired recurrent glioma samples.Periostin expression levels correlated directly with tumor grade and recurrence, and inversely with survival, in all grades of adult human glioma. Stromal deposition of periostin was detected only in grade IV gliomas. Secreted periostin promoted glioma cell invasion and adhesion, and periostin knockdown markedly impaired survival of xenografted glioma stem cells. Interactions with ?v?3 and ?v?5 integrins promoted adhesion and migration, and periostin abrogated cytotoxicity of the ?v?3/?5 specific inhibitor cilengitide. Periostin-associated gene signatures, predominated by matrix and secreted proteins, corresponded to patient prognosis and functional motifs related to increased malignancy.Periostin is a robust marker of glioma malignancy and potential tumor recurrence. Abrogation of glioma stem cell tumorigenicity after periostin inhibition provides support for exploring the therapeutic impact of targeting periostin.

SUBMITTER: Mikheev AM

PROVIDER: S-EPMC4483094 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Periostin is a novel therapeutic target that predicts and regulates glioma malignancy.

Mikheev Andrei M AM Mikheeva Svetlana A SA Trister Andrew D AD Tokita Mari J MJ Emerson Samuel N SN Parada Carolina A CA Born Donald E DE Carnemolla Barbara B Frankel Sam S Kim Deok-Ho DH Oxford Rob G RG Kosai Yoshito Y Tozer-Fink Kathleen R KR Manning Thomas C TC Silber John R JR Rostomily Robert C RC

Neuro-oncology 20140819 3

<h4>Background</h4>Periostin is a secreted matricellular protein critical for epithelial-mesenchymal transition and carcinoma metastasis. In glioblastoma, it is highly upregulated compared with normal brain, and existing reports indicate potential prognostic and functional importance in glioma. However, the clinical implications of periostin expression and function related to its therapeutic potential have not been fully explored.<h4>Methods</h4>Periostin expression levels and patterns were exam ...[more]

PMID: 25140038

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Periostin is a novel therapeutic target that predicts and regulates glioma malignancy.

Publications

Periostin is a novel therapeutic target that predicts and regulates glioma malignancy.

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