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; Melbourne Urological Research Alliance (MURAL)

doi:10.1016/j.biomaterials.2018.12.030

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

Biomaterials. 2019 Mar:197:72-85. doi: 10.1016/j.biomaterials.2018.12.030. Epub 2019 Jan 2.

Authors

Brooke A Pereira¹, Natalie L Lister¹, Kohei Hashimoto², Linda Teng¹, Maria Flandes-Iparraguirre³, Angelina Eder³, Alvaro Sanchez-Herrero³, Birunthi Niranjan¹; Melbourne Urological Research Alliance (MURAL)⁴

Collaborators

Melbourne Urological Research Alliance (MURAL):
Mark Frydenberg⁵, Melissa M Papargiris⁶, Mitchell G Lawrence⁷, Renea A Taylor⁸, Dietmar W Hutmacher⁹, Stuart J Ellem¹⁰, Gail P Risbridger¹¹, Elena M De-Juan-Pardo³

Affiliations

¹ Prostate Cancer Research Group, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, Victoria, Australia.
² Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
³ Centre in Regenerative Medicine, Institute of Health & Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
⁴ Melbourne Urological Research Alliance (MURAL), Melbourne, Victoria, Australia.
⁵ Prostate Cancer Research Group, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, Victoria, Australia; Department of Surgery, Monash University, Clayton, Victoria, Australia; Australian Urology Associates, Melbourne, Victoria, Australia.
⁶ Prostate Cancer Research Group, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, Victoria, Australia; Melbourne Urological Research Alliance (MURAL), Melbourne, Victoria, Australia.
⁷ Prostate Cancer Research Group, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, Victoria, Australia; Prostate Cancer Translational Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.
⁸ Prostate Cancer Research Group, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, Victoria, Australia; Prostate Cancer Translational Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia; Department of Physiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
⁹ Centre in Regenerative Medicine, Institute of Health & Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia; ARC Centre in Additive Biomanufacturing, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
¹⁰ School of Health and Wellbeing, University of Southern Queensland, Ipswich, Queensland, Australia.
¹¹ Prostate Cancer Research Group, Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, Victoria, Australia; Prostate Cancer Translational Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: gail.risbridger@monash.edu.

PMID: 30641266
DOI: 10.1016/j.biomaterials.2018.12.030

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 malignancy, enhanced the morphometric transition of benign epithelia via a tryptase-mediated mechanism. Our patient-specific 3D microtissues reveal a cascade of interactions between prostatic CAFs, their native ECM and mast cell-derived tryptase, rendering them important microenvironmental drivers of prostate cancer progression.

Keywords: 3D model; Cancer-associated fibroblasts; Mast cells; Melt electrowritten scaffolds; Prostate cancer; Tumour microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cancer-Associated Fibroblasts / metabolism
Cancer-Associated Fibroblasts / pathology*
Cell Line, Tumor
Cells, Cultured
Coculture Techniques
Disease Progression
Humans
Male
Mast Cells / metabolism
Mast Cells / pathology*
Prostate / metabolism
Prostate / pathology*
Prostatic Neoplasms / metabolism
Prostatic Neoplasms / pathology*
Tissue Engineering
Tissue Scaffolds / chemistry
Tryptases / metabolism*
Tumor Microenvironment

Substances

Tryptases