Cancer-associated fibroblasts of the prostate promote a compliant and more invasive phenotype in benign prostate epithelial cells

A Jaeschke; A Jacobi; M G Lawrence; G P Risbridger; M Frydenberg; E D Williams; I Vela; D W Hutmacher; L J Bray; A Taubenberger

doi:10.1016/j.mtbio.2020.100073

Cancer-associated fibroblasts of the prostate promote a compliant and more invasive phenotype in benign prostate epithelial cells

Mater Today Bio. 2020 Aug 17:8:100073. doi: 10.1016/j.mtbio.2020.100073. eCollection 2020 Sep.

Authors

A Jaeschke^{1

2}, A Jacobi^{3

4}, M G Lawrence^{5

6

7}, G P Risbridger^{5

6

7}, M Frydenberg^{5

8

9}, E D Williams^{1

10

11

12}, I Vela^{1

10

11

12

13}, D W Hutmacher^{1

2

12}, L J Bray^{1

2}, A Taubenberger³

Affiliations

¹ Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove, Australia.
² School of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology (QUT), Brisbane, Australia.
³ Biotechnology Center, Technische Universität Dresden, Germany.
⁴ Max Planck Institute for the Science of Light & Max-Planck-Zentrum für Physik und Medizin, Erlangen, Germany.
⁵ Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
⁶ Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
⁷ Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
⁸ Australian Urology Associates, Melbourne, Victoria, Australia.
⁹ Department of Urology, Cabrini Health, Malvern, Victoria, Australia.
¹⁰ Australian Prostate Cancer Research Centre-Queensland, Queensland University of Technology (QUT), Kelvin Grove, Australia.
¹¹ Translational Research Institute, Woolloongabba, Australia.
¹² School of Biomedical Sciences, Faculty of Health, Queensland University of Technology (QUT), Brisbane, Australia.
¹³ Department of Urology, Princess Alexandra Hospital, Woolloongabba, Australia.

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.

Keywords: Atomic force microscopy (AFM); Cancer-associated fibroblasts; Cell mechanics; Prostate cancer; Real-time deformability cytometry (RT-FDC); Tumor microenvironment.