Cx43 in Neural Progenitors Promotes Glioma Invasion in a 3D Culture System

International Journal of Molecular Sciences

WunChey Sin¹  Kanika Khosla¹  ChristianC. Naus¹ 

[1] Department of Cellular and Physiological Sciences, Life Sciences Institute, The University of British Columbia, BC V6T 1Z3, Vancouver, Canada;

关键词: Cx43;    glioma;    invasion;    3D;    time-lapse imaging;    human brain tumor-initiating cells;   

DOI  :  10.3390/ijms21155216

来源: DOAJ

【 摘 要 】

The environment that envelops the cancer cells intimately affects the malignancy of human cancers. In the case of glioma, an aggressive adult brain cancer, its high rate of recurrence after total resection is responsible for a poor prognosis. Connexin43 (Cx43) is a gap junction protein with a prominent presence in glioma-associated normal brain cells, specifically in the reactive astrocytes. We previously demonstrated that elimination of Cx43 in these astrocytes reduces glioma invasion in a syngeneic mouse model. To further our investigation in human glioma cells, we developed a scaffold-free 3D platform that takes into account both the tumor and its interaction with the surrounding tissue. Using cell-tracking dyes and 3D laser scanning confocal microscopy, we now report that the elimination of Cx43 protein in neural progenitor spheroids reduced the invasiveness of human brain tumor-initiating cells, confirming our earlier observation in an intact mouse brain. By investigating the glioma invasion in a defined multicellular system with a tumor boundary that mimics the intact brain environment, our findings strengthen Cx43 as a candidate target for glioma control.

【 授权许可】

Unknown