Journal article

Tissue engineered human prostate microtissues reveal key role of mast cell-derived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitro

Brooke A Pereira, Natalie L Lister, Kohei Hashimoto, Linda Teng, Maria Flandes-Iparraguirre, Angelina Eder, Alvaro Sanchez-Herrero, Birunthi Niranjan, Mark Frydenberg, Melissa M Papargiris, Mitchell G Lawrence, Renea A Taylor, Dietmar W Hutmacher, Stuart J Ellem, Gail P Risbridger, Elena M De-Juan-Pardo

Biomaterials | ELSEVIER SCI LTD | Published : 2019

Abstract

The tumour microenvironment plays a vital role in the development of solid malignancies. Here we describe an in vitro human prostate cancer microtissue model that facilitates the incorporation and interrogation of key elements of the local prostatic tumour microenvironment. Primary patient-derived cancer-associated fibroblasts (CAFs) were cultured in three-dimensional (3D) melt electrowritten scaffolds where they deposited extensive extracellular matrix (ECM) and promoted significant changes in prostate epithelial morphology, when compared to matched non-malignant prostatic fibroblasts (NPFs). The addition of mast cells, a resident prostatic immune population that is expanded during early ma..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Victorian Government through the Victorian Cancer Agency


Funding Acknowledgements

This work was partly funded by the National Health and Medical Research Council of Australia (Senior Principal Research Fellowship to GP Risbridger 1102752; Project Grant to GP Risbridger and MG Lawrence 1106870). MG Lawrence and RA Taylor were supported by the Victorian Government through the Victorian Cancer Agency (MCRF15023 and MCRF18017, respectively). BA Pereira was supported by the Australian Government Research Training Program (RTP) Scholarship. M Flandes-Iparraguirre, A Eder, A Sanchez-Herrero, DW Hutmacher and EM De-Juan-Pardo were supported by the Australian Research Council (ITTC in Additive Biomanufacturing). The authors acknowledge the generosity of Prof. Simon Hayward (Vanderbilt University, USA) for the provision of the BPH-1 cell line, Dr. Joseph Butterfield (Mayo Clinic, USA) for the provision of the HMC-1 cell line, and Dr. Arnold S. Kirshenbaum and Dr. Dean D. Metcalfe (NIAID, USA) for the provision of the LAD2 cell line. The fibronectin and collagen IV antibodies (developed by RJ Klebe and H Furthmayr respectively) were obtained from the Developmental Studies Hybridoma Bank (DSHB), created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. The authors acknowledge Neerrajah Nadarajah, Edward Ren, Jack Hampson, John Pereira and Thomas Marshall for excellent technical assistance, Dr. Ross Snow and Dr. Damien Bolton for patient recruitment, TissuPath Pathology for pathology support, the Australian Prostate Cancer BioResource for specimen collection, the Melbourne Urological Research Alliance (MURAL) for patient-derived cells, and the patients who generously donated their tissues to our research program. The authors acknowledge the facilities, scientific and technical assistance of Monash Micro Imaging, Monash University, Victoria, Australia. This work was performed in part at the Melbourne Centre for Nanofabrication (MCN) in the Victorian Node of the Australian National Fabrication Facility (ANFF). Some of the data reported in this work were obtained at the Central Analytical Research Facility (CARF) operated by the Institute for Future Environments, Queensland University of Technology (QUT). Access to CARF is supported by the Science and Engineering Faculty, QUT.