Work done in the lab of Dr. Shilpee Dutt at Tata Memorial Centre-ACTREC, Mumbai
About author
Anagha Acharekar obtained her Bachelor of Science degree in Microbiology from Ramnarain Ruia College, Mumbai, and she pursued her master’s in Medical Biotechnology from Maharaja Sayaji Rao University, Baroda. She is pursuing her Ph.D. under the mentorship of Dr. Shilpee Dutt at DNA Repair and Molecular Oncology Lab at Advanced Center for Treatment Research and Education in Cancer-TATA Memorial Centre (ACTREC-TMC), Mumbai. Her work focuses on Characterizing the phenotypic properties of recurrent populations and identifying novel therapeutic targets for recurrent GBM.
Exploring the Role of Substrate Stiffness in Aggressiveness of Recurrent Glioblastoma
Interview
How would you explain your research outcomes to the non-scientific community?
We studied how the physical substrate stiffness on which the cells grow affects the aggressiveness of recurrent glioblastoma. This study helped us to discover that when parent and recurrent GBM cells were grown on a substrate with brain-like stiffness, the recurrent cells were more aggressive than the parent cells. This aggressive phenotype was not captured when the cells were grown on plastic Petri dishes, a standard method used to culture the cells in vitro. This highlights the importance of considering the mechanosignals a cell receives when growing in its native environment. We also verified these findings in-vivo using GBM mouse models. We showed that the recurrent cells could remodel their microenvironment such that the mice’s brains became stiffer, thus promoting the aggressiveness of cancer. This model system was also able to recapitulate clinical trial results of the afatinib drug, where the patient survival outcome was not affected significantly. However, using our model system, we identified a protein, PLEKHA7, that was significantly upregulated in recurrent cells grown on 0.5kPa and was also found to be high in recurrent GBM patient biopsies. PLEKHA7 knockdown reduced the invasion and survival of recurrent GBM cells, suggesting that it could be a potential target for recurrent GBM.
How do these findings contribute to your research area?
Our study has made an essential point that it is crucial to consider the stiffness on which we grow the cells. Just by mimicking the tensile properties of a brain were able to capture the phenotypic differences between parent and recurrent GBM in in-vitro settings. Substrate stiffness plays a vital role in deciding the cell fate and hence should not be ignored.
“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?
It was also amazing to see our in-vitro results being recapitulated in in-vivo settings. We could even see that the cells grown on our model system formed stiff tumors in the mice’s brains compared to the tissue culture-grown cells, whose tumors did not have different tensile properties.
What do you hope to do next?
This work has sparked my interest in studying cell adhesion and cell-ECM interaction in more depth. I want to explore this field further to learn its role in cell signaling and fate.
Where do you seek scientific inspiration from?
I was introduced to Dr. Richard Feynman through a book called ‘Surely you’re Joking Mr. Feynman.’ I was in awe of his personality and his ability to simplify science for ordinary people. His passion for teaching has always inspired me to date. Many such non-fiction science books and Ted talks are my continuous source of inspiration. Moreover, all those professors and mentors who have inculcated critical thinking have played a pivotal role in inspiring me to pursue research.
How do you intend to help Indian science improve?
As Abdul Kalam has said, “Science has to reach the common man, and we have to create an atmosphere of scientific temper in the country.” Talking to young minds to inspire and encourage curiosity would make a difference. I would like to influence the young minds of our country and instigate inquisitiveness in them.
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. doi: 10.1016/j.matbio.2022.12.002. Epub 2022 Dec 21. PMID: 36563706. https://www.sciencedirect.com/science/article/pii/S0945053X22001494?via%3Dihub
Copy Editor: Kshipra S. Kapoor
For interview related queries, write to us at interview.biopatrika@gmail.com
