2021年1月
Mesenchymal glioblastoma-induced mature de-novo vessel formation of vascular endothelial cells in a microfluidic device
Molecular Biology Reports
- 巻
- 48
- 号
- 1
- 開始ページ
- 395
- 終了ページ
- 403
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1007/s11033-020-06061-7
- 出版者・発行元
- Springer Science and Business Media LLC
<title>Abstract</title>High vascularization is a biological characteristic of glioblastoma (GBM); however, an <italic>in-vitro</italic> experimental model to verify the mechanism and physiological role of vasculogenesis in GBM is not well-established. Recently, we established a self-organizing vasculogenic model using human umbilical vein endothelial cells (HUVECs) co-cultivated with human lung fibroblasts (hLFs). Here, we exploited this system to establish a realistic model of vasculogenesis in GBM. We developed two polydimethylsiloxane (PDMS) devices, a doughnut-hole dish and a 5-lane microfluidic device to observe the contact-independent effects of glioblastoma cells on HUVECs. We tested five patient-derived and five widely used GBM cell lines. Confocal fluorescence microscopy was used to observe the morphological changes in Red Fluorescent Protein (RFP)-HUVECs and fluorescein isothiocyanate (FITC)-dextran perfusion. The genetic and expression properties of GBM cell lines were analyzed. The doughnut-hole dish assay revealed KNS1451 as the only cells to induce HUVEC transformation to vessel-like structures, similar to hLFs. The 5-lane device assay demonstrated that KNS1451 promoted the formation of a vascular network that was fully perfused, revealing the functioning luminal construction. Microarray analysis revealed that KNS1451 is a mesenchymal subtype of GBM. Using a patient-derived mesenchymal GBM cell line, mature <italic>de-novo</italic> vessel formation could be induced in HUVECs by contact-independent co-culture with GBM in a microfluidic device. These results support the development of a novel in vitro research model and provide novel insights in the neovasculogenic mechanism of GBM and may potentially facilitate the future detection of unknown molecular targets.
- リンク情報
-
- DOI
- https://doi.org/10.1007/s11033-020-06061-7
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000604190000004&DestApp=WOS_CPL
- URL
- http://link.springer.com/content/pdf/10.1007/s11033-020-06061-7.pdf
- URL
- http://link.springer.com/article/10.1007/s11033-020-06061-7/fulltext.html
- ID情報
-
- DOI : 10.1007/s11033-020-06061-7
- ISSN : 0301-4851
- eISSN : 1573-4978
- Web of Science ID : WOS:000604190000004