TY - JOUR
T1 - Periostin is expressed by pericytes and is crucial for angiogenesis in glioma
AU - Huizer, Karin
AU - Zhu, Changbin
AU - Chirifi, Ihsan
AU - Krist, Bart
AU - Zorgman, Denise
AU - van der Weiden, Marcel
AU - van den Bosch, Thierry P.P.
AU - Dumas, Jasper
AU - Cheng, Caroline
AU - Kros, Johan M.
AU - Mustafa, Dana A.
N1 - Funding Information:
This study was partly sponsored by the China Scholarship Council (CSC) at the Erasmus Medical Center, Rotterdam, The Netherlands. The authors thank Mr. F. van der Panne for his assistance with the photography, and the laboratory staff of the Department of Experimental Cardiology of the Erasmus Medical Center for their help and provision of the blood vessel culture systems. Mrs. Vanja de Weerd is thanked for her technical assistance.
Publisher Copyright:
© 2020 American Association of Neuropathologists, Inc. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - The expression of the matricellular protein periostin has been associated with glioma progression. In previous work we found an association of periostin with glioma angiogenesis. Here, we screen gliomas for POSTN expression and identify the cells that express periostin in human gliomas. In addition, we study the role of periostin in an in vitro model for angiogenesis. The expression of periostin was investigated by RT-PCR and by immunohistochemistry. In addition, we used double labeling and in situ RNA techniques to identify the expressing cells. To investigate the function of periostin, we silenced POSTN in a 3D in vitro angiogenesis model. Periostin expression was elevated in pilocytic astrocytoma and glioblastoma, but not in grade II/III astrocytomas and oligodendrogliomas. The expression of periostin colocalized with PDGFRβ+ cells, but not with OLIG2+/SOX2+ glioma stem cells. Silencing of periostin in pericytes in coculture experiments resulted in attenuation of the numbers and the length of the vessels formation and in a decrease in endothelial junction formation. We conclude that pericytes are the main source of periostin in human gliomas and that periostin plays an essential role in the growth and branching of blood vessels. Therefore, periostin should be explored as a novel target for developing anti-angiogenic therapy for glioma.
AB - The expression of the matricellular protein periostin has been associated with glioma progression. In previous work we found an association of periostin with glioma angiogenesis. Here, we screen gliomas for POSTN expression and identify the cells that express periostin in human gliomas. In addition, we study the role of periostin in an in vitro model for angiogenesis. The expression of periostin was investigated by RT-PCR and by immunohistochemistry. In addition, we used double labeling and in situ RNA techniques to identify the expressing cells. To investigate the function of periostin, we silenced POSTN in a 3D in vitro angiogenesis model. Periostin expression was elevated in pilocytic astrocytoma and glioblastoma, but not in grade II/III astrocytomas and oligodendrogliomas. The expression of periostin colocalized with PDGFRβ+ cells, but not with OLIG2+/SOX2+ glioma stem cells. Silencing of periostin in pericytes in coculture experiments resulted in attenuation of the numbers and the length of the vessels formation and in a decrease in endothelial junction formation. We conclude that pericytes are the main source of periostin in human gliomas and that periostin plays an essential role in the growth and branching of blood vessels. Therefore, periostin should be explored as a novel target for developing anti-angiogenic therapy for glioma.
KW - Angiogenesis
KW - Glioblastoma
KW - Glioma
KW - Matricellular protein
KW - Periostin
KW - Vasculogenesis
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U2 - 10.1093/jnen/nlaa067
DO - 10.1093/jnen/nlaa067
M3 - Article
C2 - 32647861
AN - SCOPUS:85088493669
SN - 0022-3069
VL - 79
SP - 863
EP - 872
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 8
ER -