Abstract

Periostin is a secreted protein that is highly expressed in glioblastoma cells as compared to normal brain tissue, and is therefore considered as a potential biomarker in therapeutic modalities. Its contribution in the cancer cells invasive phenotype is, however, poorly understood. This work investigates the role of periostin in U-87 MG glioblastoma cell invasion, cell migration and in Transforming Growth Factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT). Periostin gene silencing, using small interfering RNA, decreased TGF-β-induced mesenchymal marker expression of fibronectin and vimentin, partly through reduced Smad2, Akt and Fak phosphorylation as well as U-87 MG cell invasion and migration. The effects of anthocyanidins, the most abundant diet-derived flavonoids, were examined on periostin-mediated downstream signaling pathways. Anthocyanidins were found to decrease periostin expression whether added under pre-, co- or post-treatment conditions along with TGF-β, and altered the Akt and Fak signaling pathways. These effects were similar to Galunisertib (LY2157299), a small molecule inhibitor of the TGF-β receptor I kinase. Taken together, our data demonstrate that periostin acts as a central element in TGF-β-induced EMT, which can be prevented by diet-derived anthocyanidins.

Highlights

  • Periostin, originally named osteoblast-specific factor-2 (Osf2), is a 93.3 kDa matricellular protein known to play roles in osteology and tissue repair in the cardiovascular and respiratory systems [1]

  • We measured the effects of Transforming Growth Factor β (TGF-β) on periostin expression in U-87 MG cells and found that it induced the expression of periostin in a time-dependant manner (Figure 1A) to reach a plateau at 10 ng/mL TGF-β (Figure 1B)

  • These results demonstrate that periostin is efficiently regulated upon TGF-β-mediated signaling in U-87 MG cells

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Summary

Introduction

Originally named osteoblast-specific factor-2 (Osf2), is a 93.3 kDa matricellular protein known to play roles in osteology and tissue repair in the cardiovascular and respiratory systems [1]. It is involved in tumor development where it promotes cancer cell survival, invasion, migration and angiogenesis leading to epithelial-mesenchymal transition (EMT) and metastasis [2]. Studies suggest that the molecular processes involved in metastasis, invasion and cell survival may be regulated through periostin functions [4]. Several studies have suggested that periostin expression and its secretion, driven by TGF-β, play a role as an EMT inducer [8]

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