Volume electron microscopy of 3D cancer cell spheroids reveals significant morphological differences compared to 2D cell cultures.

The tumorsphere, a 3D cell culture or spheroid derived from cancer stem cells, represents a valuable tool in cancer research and drug discovery due to its architecture closely resembling the physiological characteristics of in vivo tumors.

A recent article featured in the Journal of Structural Biology explored the ultrastructural morphological differences between tumorspheres and traditional monolayer cultured cells. This study utilized advanced sample preparation methodologies, including high-pressure freezing and freeze substitution, to preserve cellular structures in their native state. The images were captured using serial block-face scanning electron microscopy (SBF-SEM) with ZEISS Sigma FE-SEM.

The research was led by Dr. Mihnea Bostina, whose titles include Associate Professor at the University of Otago, Electron Microscopy Academic Lead at the Otago Micro and Nanoscale Imaging Facility, and President of Microscopy New Zealand. Collaborating on this endeavor were members of the Bostina Lab, including Nickhil Jadav, a PhD student specializing in structural oncology research within the Department of Microbiology and Immunology at the University of Otago, and Sailakshmi Velamoor, a former postdoctoral researcher at the University of Otago.

The application of SBF-SEM by this collaborative team revealed clear examples of critical morphological differences between tumorspheres and traditional 2D cell cultures. This not only reinforces the evidence supporting the superior in vivo modeling capabilities of 3D cultures but also underscores the profound insights that ultrastructural investigations with volume electron microscopy can uncover. These findings hold great promise for advancing our understanding of cancer biology and may have far-reaching implications for drug discovery and therapeutic development.

Our goal was to use SBF-SEM to explore tumorspheres' ultrastructure as they are known for being a superior cancer model compared to traditional 2D cell monolayers. The key question was how the 3D construction of cells in tumorspheres compared to those attached to a surface.

We believe that volume electron microscopy with SBF-SEM will be highly valuable for comparing different types of cancer and examining tumorsphere responses to various cancer drugs or novel therapeutic agents.