Unveiling the Influence of Tumor Microenvironment and Spatial Heterogeneity on Temozolomide Resistance in Glioblastoma Using an Advanced Human In Vitro Model of the Blood‐Brain Barrier and Glioblastoma

Page view(s)
282
Checked on Apr 18, 2024
Unveiling the Influence of Tumor Microenvironment and Spatial Heterogeneity on Temozolomide Resistance in Glioblastoma Using an Advanced Human In Vitro Model of the Blood‐Brain Barrier and Glioblastoma
Title:
Unveiling the Influence of Tumor Microenvironment and Spatial Heterogeneity on Temozolomide Resistance in Glioblastoma Using an Advanced Human In Vitro Model of the Blood‐Brain Barrier and Glioblastoma
Journal Title:
Small
Publication Date:
31 August 2023
Citation:
Lam, M. S., Aw, J. J., Tan, D., Vijayakumar, R., Lim, H. Y. G., Yada, S., Pang, Q. Y., Barker, N., Tang, C., Ang, B. T., Sobota, R. M., & Pavesi, A. (2023). Unveiling the Influence of Tumor Microenvironment and Spatial Heterogeneity on Temozolomide Resistance in Glioblastoma Using an Advanced Human In Vitro Model of the Blood‐Brain Barrier and Glioblastoma. Small. Portico. https://doi.org/10.1002/smll.202302280
Abstract:
AbstractGlioblastoma (GBM) is the most common primary malignant brain cancer in adults with a dismal prognosis. Temozolomide (TMZ) is the first‐in‐line chemotherapeutic; however, resistance is frequent and multifactorial. While many molecular and genetic factors have been linked to TMZ resistance, the role of the solid tumor morphology and the tumor microenvironment, particularly the blood‐brain barrier (BBB), is unknown. Here, the authors investigate these using a complex in vitro model for GBM and its surrounding BBB. The model recapitulates important clinical features such as a dense tumor core with tumor cells that invade along the perivascular space; and a perfusable BBB with a physiological permeability and morphology that is altered in the presence of a tumor spheroid. It is demonstrated that TMZ sensitivity decreases with increasing cancer cell spatial organization, and that the BBB can contribute to TMZ resistance. Proteomic analysis with next‐generation low volume sample workflows of these cultured microtissues revealed potential clinically relevant proteins involved in tumor aggressiveness and TMZ resistance, demonstrating the utility of complex in vitro models for interrogating the tumor microenvironment and therapy validation.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the Agency for Science Technology and Research - Career Development Fund
Grant Reference no. : C210112058

This research / project is supported by the National Medical Research Council, Singapore - Translational and Clinical Research Flagship Programme - Tier 1
Grant Reference no. : NMRC/ TCR/016-NNI/2016

This research / project is supported by the National Medical Research Council, Singapore - Open Fund-Large Collaborative Grant
Grant Reference no. : MOH-000541-00

This research is supported by core funding from: Institute of Molecular and Cell Biology
Grant Reference no. : SC15-R0039
Description:
ISSN:
1613-6810
1613-6829