15th Annual Symposium
Physics of Cancer
Leipzig, Germany
Sept. 30 - Oct. 2, 2024
Invited Talk
Prostate cancer associated fibroblasts have distinct morpho-mechanical features that are associated with patient outcome
Anna Taubenberger1,2, Antje Garside1,2, Angela Jacobi1,2, Shivakumar Keerthikumar3,4,5,6, Michelle Richards3, Birunthi Niranjan3, Linda Teng3, Gail Risbridger3,4,5,6, Vaibhav Mahajan1,2, Nicolas Choo3, Mitch Lawrence3,4,5,6,7
1Center for Molecular and Cellular Bioengineering (CMCB), BIOTEC, TUD, Dresden University of Technology, Dresden, Germany
2Leibniz-Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials, Dresden, Germany
3Melbourne Urological Research Alliance, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
4Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
5Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia
6Cabrini Institute, Cabrini Health, Malvern, Victoria, Australia
7Department of Physiology, Biomedicine Discovery Institute Cancer Program, Monash University, Clayton, Victoria, Australia
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Prostate cancer (PCa) ranges among the most commonly diagnosed types of cancer and remains
a major health burden worldwide. Despite multiple established therapies, there persists a lack
of knowledge of the underlying factors that contribute to disease progression, and clearly better
prognostic tools that allow for earlier interventions are needed. A key role in tumor progression
has been attributed to the tumor stroma including its cellular components such as cancer
associated fibroblasts (CAFs). Here we present a comprehensive study where we quantitatively
assessed morpho-mechanical properties of patient-derived prostatic CAFs and matched normal
prostatic fibroblasts from a cohort of 35 patients, through a combination of morphometric
analysis on microscopy images and real-time deformability cytometry, a high-throughput
technique for probing single cell morphological and mechanical properties. We demonstrate
that CAFs comprise distinct morphological and mechanical features compared to their normal
counterparts, including nuclear size and shape, F-actin cytoskeletal arrangement, as well as
cellular volumes and elastic properties. Remarkably, a combined score of afore-mentioned
mechanical and morphological parameter was able to distinguish patients with shorter and
longer time of clinical relapse. In addition, morpho-mechanical changes across patients were
correlated with alterations in cellular components and pathways revealed in transcriptomic
datasets. Finally, we show that commonly used clinical drugs and tool compounds interfering
with signaling pathways or perturbing single cytoskeletal elements affect the morphological
and mechanical properties of CAFs. In summary, our results show that high-throughput
assessments of the biophysical properties of stromal components can potentially serve as a
complementary tool to predict patient outcome.
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