Glioblastoma multiforme (GBM) stands as a formidable challenge in the realm of brain cancer, marked by a grim prognosis even in the face of rigorous treatment protocols. Despite initial surgical intervention and radiation, the tumor invariably resurfaces within a few months, showcasing a relentless and aggressive phenotype. While researchers have delved into the influence of microenvironment on various tumors, including GBM, the impact of mechanical factors on radio-recurrent GBM tumors remains largely unexplored.
In an effort to unravel this enigma, our study focused on elucidating the influence of mechanical signals on the behavior of GBM cells both pre- and post-radiation. Strikingly, we observed a profound disparity in the mechanosensing mechanisms between these two populations. Specifically, when subjected to a microenvironment mimicking the stiffness of the brain, the post-radiation cell population exhibited heightened levels of migration, invasion, drug resistance, and in vivo tumorigenicity—patterns often observed clinically.
Interestingly, these disparities were negligible or absent when the cells were cultured on stiffer substrates, such as conventional plastic plates.
To emulate the in vivo microenvironment further, we employed a novel self-assembly method to create 3D tumoroids on soft substrates. This approach revealed that our 3D tumoroid formation technique effectively captures various in vivo-like phenotypes.
In essence, our ongoing study underscores the critical importance of exploring physical parameters in comprehending the intricacies of biological systems within the context of serious diseases. This holistic approach may pave the way for a deeper understanding of GBM and potentially inform novel therapeutic strategies.
This work has been performed by Dr. Pallavi Shirke of Ms. Ketaki Bachal from MLab IITB, in collaboration with Prof. Shilpee Dutt from ACTREC and her students Dr. Anagha Achrekar and Ms. Debashmita Sarkar.