Exploring the Role of Substrate Stiffness in Aggressiveness of Recurrent Glioblastoma
Author Interview: Anagha Acharekar obtained her B.Sc. in Microbiology from Ramnarain Ruia College, Mumbai, and an M.Sc. in Medical Biotechnology from Maharaja Sayaji Rao University, Baroda. She is pursuing her Ph.D. under the mentorship of Dr. Shilpee Dutt at the DNA Repair and Molecular Oncology Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC-TMC), Mumbai. Her research focuses on characterizing the phenotypic properties of recurrent GBM and identifying novel therapeutic targets.
Research conducted in: Dr. Shilpee Dutt’s Lab, Tata Memorial Centre – ACTREC, Mumbai
🎙️ Interview
How would you explain your research outcomes to the non-scientific community?
We studied how the physical stiffness of the substrate on which cells grow affects the aggressiveness of recurrent glioblastoma (GBM). When parent and recurrent GBM cells were grown on a substrate mimicking brain-like softness, the recurrent cells exhibited more aggressive behavior than the parent ones. However, this difference was not observed when using standard plastic Petri dishes—highlighting the importance of cellular mechanosignals.
We validated this finding in vivo using mouse models, where recurrent GBM cells remodeled the brain to become stiffer, further promoting tumor aggression. Interestingly, our model also matched clinical trial results of the drug afatinib, which showed limited survival benefit. Most notably, we identified a protein, PLEKHA7, significantly upregulated in recurrent GBM cells. Its knockdown reduced both invasion and survival, suggesting it as a potential therapeutic target.
How do these findings contribute to your research area?
Our study underscores the importance of mimicking physiological stiffness in in-vitro models. By replicating brain-like conditions, we captured phenotypic differences between parent and recurrent GBM that were otherwise missed. Substrate stiffness significantly impacts cell fate and should not be overlooked.
“Our study has made an essential point that it is crucial to consider the stiffness on which we grow the cells.”
What was the exciting moment during your research?
Seeing our in-vitro findings recapitulated in in-vivo models was truly exciting. The tumors formed by cells grown on soft substrates had altered tensile properties, validating the physiological relevance of our approach.
What do you hope to do next?
This work piqued my interest in cell adhesion and cell–ECM interactions. I want to further explore their roles in cell signaling and fate determination.
Where do you seek scientific inspiration from?
I was inspired by Richard Feynman through his book Surely You’re Joking, Mr. Feynman. His ability to simplify complex science and his passion for teaching continue to inspire me. TED talks, non-fiction science books, and professors who encouraged critical thinking have also greatly influenced my path.
How do you intend to help Indian science improve?
As Dr. A.P.J. Abdul Kalam said, “Science has to reach the common man.” I believe inspiring young minds and fostering curiosity will help build a strong scientific temper in India. I aim to play my part in this journey.
📄 Reference
Acharekar A, Bachal K, Shirke P, Thorat R, Banerjee A, Gardi N, Majumder A, Dutt S.
Substrate stiffness regulates the recurrent glioblastoma cell morphology and aggressiveness.
Matrix Biol. 2023 Jan;115:107–127.
Read full article
Copy Editor: Kshipra S. Kapoor
📬 For interview-related queries, write to us at interview.biopatrika@gmail.com
🔗 Check the Latest Updates on BioPatrika
Explore more from our platform by visiting these dedicated sections:
