Periostin (POSTN) Regulates Tumor Resistance to Antiangiogenic Therapy in Glioma Models

Abstract

Periostin (POSTN) interacts with multiple integrins to coordinate a variety of cellular processes, including epithelial-to-mesenchymal transition (EMT) and cell migration. In our previous study, anti-vascular endothelial growth factor A (VEGF-A) therapy was associated with resistance and EMT. The present study sought to determine the role of POSTN in the resistance of glioma stem cells (GSCs) 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 transforming growth factor beta-1 (TGF beta1) and hypoxia-inducible factor-1 alpha (HIF1 alpha) in GSCs. At the molecular level, POSTN regulated invasion and expression of EMT (caveolin-1) and angiogenesis-related genes (HIF1 alpha and VEGF-A) through activation of signal transducer and activator of transcription 3 (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.

Increased concentration of serum periostin is associated with poor outcome of patients with aneurysmal subarachnoid hemorrhage

“…Matsunaga et al reported that periostin was expressed at higher level in primate cerebral cortex than mouse cerebral cortex and periostin exhibited neurite outgrowth activity in brain tissues . Recent studies have revealed that periostin was overexpressed in neural stem cell (NSCs) following hypoxia ischemia and hypoxia could increased periostin expression . Hypoxia, oxidative stress and inflammatory reaction could be involved in the pathological processes of traumatic brain injury (TBI) and stroke, so periostin was supposed to elevated in these neurological diseases.…”

Commentary: Periostin (POSTN) Regulates Tumor Resistance to Antiangiogenic Therapy in Glioma Models

“…In this current study, we investigated the relationship between POSTN expression and bevacizumab resistance in mouse glioma stem cells xenograft tumors. In our model of anti-VEGF-A resistance 3 , GSC11 and U87 tumors treated with bevacizumab expressed higher POSTN levels than control tumors. Periostin (POSTN; osteoblastspecific factor 2) is a 90-kDa ECM protein containing an amino-terminal EMI domain, tandem repeats of four fasciclin domains, and a carboxyterminal (C-terminal) domain, including a heparin binding site 5 .…”

“…Studies suggest mesenchymal transition and hypoxia signaling as two major pathways associated with the development of resistance to anti-VEGF therapy. Recently, we reported that the glioma treated with bevacizumab have higher periostin (POSTN) expression than control tumors in a murine glioma tumor models 3 . In this commentary, we review our recent findings as well as the role of POSTN in antiangiogenic therapy resistance in glioma.…”

Periostin and CA242 as potential diagnostic serum biomarkers complementing CA19.9 in detecting pancreatic cancer

“…Periostin is a secreted matrix N‐glycoprotein that plays vital roles in numerous cancers, especially in gastrointestinal malignancy . For pancreatic cancer, it is reported that POSTN has a biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells, participates in the process of tumor angiogenesis, and could promote invasiveness and resistance of pancreatic cancer cells to induce cell death .…”