Projects per year
Abstract
Reciprocal interactions between prostate epithelial cells and their adjacent stromal microenvironment not only are essential for tissue homeostasis but also play a key role in tumor development and progression. Malignant transformation is associated with the formation of a reactive stroma where cancer-associated fibroblasts (CAFs) induce matrix remodeling and thereby provide atypical biochemical and biomechanical signals to epithelial cells. Previous work has been focused on the cellular and molecular phenotype as well as on matrix stiffness and remodeling, providing potential targets for cancer therapeutics. So far, biomechanical changes in CAFs and adjacent epithelial cells of the prostate have not been explored. Here, we compared the mechanical properties of primary prostatic CAFs and patient-matched non-malignant prostate tissue fibroblasts (NPFs) using atomic force microscopy (AFM) and real-time deformability cytometry (RT-FDC). It was found that CAFs exhibit an increased apparent Young's modulus, coinciding with an altered architecture of the cytoskeleton compared with NPFs. In contrast, co-cultures of benign prostate epithelial (BPH-1) cells with CAFs resulted in a decreased stiffness of the epithelial cells, as well as an elongated morphological phenotype, when compared with co-cultures with NPFs. Moreover, the presence of CAFs increased proliferation and invasion of epithelial cells, features typically associated with tumor progression. Altogether, this study provides novel insights into the mechanical interactions between epithelial cells with the malignant prostate microenvironment, which could potentially be explored for new diagnostic approaches.
Original language | English |
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Article number | 100073 |
Number of pages | 14 |
Journal | Materials Today Bio |
Volume | 8 |
DOIs | |
Publication status | Published - Sept 2020 |
Keywords
- Atomic force microscopy (AFM)
- Cancer-associated fibroblasts
- Cell mechanics
- Prostate cancer
- Real-time deformability cytometry (RT-FDC)
- Tumor microenvironment
Projects
- 1 Finished
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NHMRC Research Fellowship
National Health and Medical Research Council (NHMRC) (Australia)
9/03/01 → 31/12/20
Project: Research
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Equipment
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Histology Platform
Camilla Cohen (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility