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

Andrei M. Mikheev; Svetlana A. Mikheeva; Andrew D. Trister; Mari J. Tokita; Samuel N. Emerson; Carolina A. Parada; Donald E. Born; Barbara Carnemolla; Sam Frankel; Deok Ho Kim; Rob G. Oxford; Yoshito Kosai; Kathleen R. Tozer-Fink; Thomas C. Manning; John R. Silber; Robert C. Rostomily

doi:10.1093/neuonc/nou161

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

Andrei M. Mikheev, Svetlana A. Mikheeva, Andrew D. Trister, Mari J. Tokita, Samuel N. Emerson, Carolina A. Parada, Donald E. Born, Barbara Carnemolla, Sam Frankel, Deok Ho Kim, Rob G. Oxford, Yoshito Kosai, Kathleen R. Tozer-Fink, Thomas C. Manning, John R. Silber, Robert C. Rostomily

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

Abstract

Background. 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. Methods. 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. Results. 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 avb3 and avb5 integrins promoted adhesion and migration, and periostin abrogated cytotoxicity of the avb3/b5 specific inhibitor cilengitide. Periostin-associated gene signatures, predominated by matrix and secreted proteins, corresponded to patient prognosis and functional motifs related to increased malignancy. Conclusion. 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.

Original language	English (US)
Pages (from-to)	372-382
Number of pages	11
Journal	Neuro-oncology
Volume	17
Issue number	3
DOIs	https://doi.org/10.1093/neuonc/nou161
State	Published - Mar 2015

Keywords

Glioma stem cells
Invasion
Malignancy
Periostin
Recurrent glioma

ASJC Scopus subject areas

Oncology
Clinical Neurology
Cancer Research

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Mikheev, A. M., Mikheeva, S. A., Trister, A. D., Tokita, M. J., Emerson, S. N., Parada, C. A., Born, D. E., Carnemolla, B., Frankel, S., Kim, D. H., Oxford, R. G., Kosai, Y., Tozer-Fink, K. R., Manning, T. C., Silber, J. R., & Rostomily, R. C. (2015). Periostin is a novel therapeutic target that predicts and regulates glioma malignancy. Neuro-oncology, 17(3), 372-382. https://doi.org/10.1093/neuonc/nou161

Mikheev, AM, Mikheeva, SA, Trister, AD, Tokita, MJ, Emerson, SN, Parada, CA, Born, DE, Carnemolla, B, Frankel, S, Kim, DH, Oxford, RG, Kosai, Y, Tozer-Fink, KR, Manning, TC, Silber, JR & Rostomily, RC 2015, 'Periostin is a novel therapeutic target that predicts and regulates glioma malignancy', Neuro-oncology, vol. 17, no. 3, pp. 372-382. https://doi.org/10.1093/neuonc/nou161

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title = "Periostin is a novel therapeutic target that predicts and regulates glioma malignancy",

abstract = "Background. 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. Methods. 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. Results. 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 avb3 and avb5 integrins promoted adhesion and migration, and periostin abrogated cytotoxicity of the avb3/b5 specific inhibitor cilengitide. Periostin-associated gene signatures, predominated by matrix and secreted proteins, corresponded to patient prognosis and functional motifs related to increased malignancy. Conclusion. 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.",

keywords = "Glioma stem cells, Invasion, Malignancy, Periostin, Recurrent glioma",

author = "Mikheev, {Andrei M.} and Mikheeva, {Svetlana A.} and Trister, {Andrew D.} and Tokita, {Mari J.} and Emerson, {Samuel N.} and Parada, {Carolina A.} and Born, {Donald E.} and Barbara Carnemolla and Sam Frankel and Kim, {Deok Ho} and Oxford, {Rob G.} and Yoshito Kosai and Tozer-Fink, {Kathleen R.} and Manning, {Thomas C.} and Silber, {John R.} and Rostomily, {Robert C.}",

note = "Funding Information: National Institutes of Health R01CA136808 (to R.C.R), R21NS082542 (to A.M.M.) and U54CA149237 (A.D.T.), T32GM007454 (M.J.T.), the Fred Hutchinson/University of Washington Cancer Consortium pilot grant, and Tietze Stem Cell Scientist Award (to R.C.R.). Publisher Copyright: {\textcopyright} The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved.",

year = "2015",

month = mar,

doi = "10.1093/neuonc/nou161",

language = "English (US)",

volume = "17",

pages = "372--382",

journal = "Neuro-oncology",

issn = "1522-8517",

publisher = "Oxford University Press",

number = "3",

}

TY - JOUR

T1 - Periostin is a novel therapeutic target that predicts and regulates glioma malignancy

AU - Mikheev, Andrei M.

AU - Mikheeva, Svetlana A.

AU - Trister, Andrew D.

AU - Tokita, Mari J.

AU - Emerson, Samuel N.

AU - Parada, Carolina A.

AU - Born, Donald E.

AU - Carnemolla, Barbara

AU - Frankel, Sam

AU - Kim, Deok Ho

AU - Oxford, Rob G.

AU - Kosai, Yoshito

AU - Tozer-Fink, Kathleen R.

AU - Manning, Thomas C.

AU - Silber, John R.

AU - Rostomily, Robert C.

N1 - Funding Information: National Institutes of Health R01CA136808 (to R.C.R), R21NS082542 (to A.M.M.) and U54CA149237 (A.D.T.), T32GM007454 (M.J.T.), the Fred Hutchinson/University of Washington Cancer Consortium pilot grant, and Tietze Stem Cell Scientist Award (to R.C.R.). Publisher Copyright: © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved.

PY - 2015/3

Y1 - 2015/3

N2 - Background. 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. Methods. 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. Results. 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 avb3 and avb5 integrins promoted adhesion and migration, and periostin abrogated cytotoxicity of the avb3/b5 specific inhibitor cilengitide. Periostin-associated gene signatures, predominated by matrix and secreted proteins, corresponded to patient prognosis and functional motifs related to increased malignancy. Conclusion. 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.

AB - Background. 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. Methods. 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. Results. 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 avb3 and avb5 integrins promoted adhesion and migration, and periostin abrogated cytotoxicity of the avb3/b5 specific inhibitor cilengitide. Periostin-associated gene signatures, predominated by matrix and secreted proteins, corresponded to patient prognosis and functional motifs related to increased malignancy. Conclusion. 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.

KW - Glioma stem cells

KW - Invasion

KW - Malignancy

KW - Periostin

KW - Recurrent glioma

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DO - 10.1093/neuonc/nou161

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EP - 382

JO - Neuro-oncology

JF - Neuro-oncology

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ER -

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

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Keywords

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