Periostin (POSTN) regulates tumor resistance to antiangiogenic therapy in glioma models

Soon Young Park, Yuji Piao, Kang Jin Jeong, Jianwen Dong, John F. De Groot

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Periostin (POSTN) interacts with multiple integrins to coordinate a variety of cellular processes, including epithelialto-mesenchymal transition (EMT) and cell migration. In our previous study, anti-VEGF-A therapy was associated with resistance and EMT. This study sought to determine the role of POSTN in the resistance of glioma stem cells (GSC) to antiangiogenic therapy. In mouse xenograft models of human glioma, POSTN expression was associated with acquired resistance to anti-VEGF-A therapy and had a synergistic effect with bevacizumab in prolonging survival and decreasing tumor volume. Resistance to anti-VEGF-A therapy regulated by POSTN was associated with increased expression of TGFβ1 and hypoxia-inducible factor-1a (HIF1α) in GSCs. At the molecular level, POSTN regulated invasion and expression of EMT (caveolin-1) and angiogenesis-related genes (HIF1a and VEGF-A) through activation of STAT3. Moreover, recombinant POSTN increased GSC invasion. Collectively, our findings suggest that POSTN plays an important role in glioma invasion and resistance to antiangiogenic therapy.

Original languageEnglish (US)
Pages (from-to)2187-2197
Number of pages11
JournalMolecular cancer therapeutics
Volume15
Issue number9
DOIs
StatePublished - Sep 2016
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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