Endothelium-induced three-dimensional invasion of heterogeneous glioma initiating cells in a microfluidic coculture platform

Yuta Chonan, Sotaro Taki, Oltea Sampetrean, Hideyuki Saya, Ryo Sudo

研究成果: Article査読

25 被引用数 (Scopus)

抄録

Glioblastoma (GBM) is a highly invasive primary brain tumor that displays cellular heterogeneity, which is composed of glioma initiating cells (GICs) and their differentiated progeny. GICs play an important role in driving aggressive invasion. In particular, the interaction between GICs and blood vessels is critical because blood vessels are known to serve as routes for the invasion of GICs. However, the effect of endothelial cells on the three-dimensional (3D) invasion process of GICs as well as the spatial relationship between GICs and their differentiated progeny remains unclear. Here, we utilized a microfluidic device to recapitulate the 3D brain tumor microenvironments constituted by human umbilical vein endothelial cells (HUVECs) and type I collagen. Using the device, we found that HUVECs promoted the 3D invasion of heterogeneous glioma cell populations into type I collagen gel. The invasion induced by HUVECs was predominantly preceded by cells positive for nestin, a neural stem cell marker. In contrast, cells positive for tubulin β3 (TUBB3), a differentiated cell marker, rarely preceded invasion. In addition, HUVECs induced the upregulation of TUBB3 in GICs. Finally, we found that the genes associated with invasion, such as integrins α2 and β3, were significantly upregulated in the presence of HUVECs. These results as well as the experimental approach provide valuable knowledge for the development of effective therapeutic strategies targeting the aggressive invasion of GBM.

本文言語English
ページ(範囲)762-773
ページ数12
ジャーナルIntegrative Biology (United Kingdom)
9
9
DOI
出版ステータスPublished - 2017 9

ASJC Scopus subject areas

  • 生物理学
  • 生化学

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