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

Pereira, Brooke A. and Lister, Natalie L. and Hashimoto, Kohei and Teng, Linda and Flandes-Iparraguirre, Maria and Eder, Angelina and Sanchez-Herrero, Alvaro and Niranjan, Birunthi and Melbourne Urological Research Alliance (MURAL), and Frydenberg, Mark and Papargiris, Melissa M. and Lawrence, Mitchell G. and Taylor, Renea A. and Hutmacher, Dietmar W. and Ellem, Stuart J. and Risbridger, Gail P. and De-Juan-Pardo, Elena M. (2019) Tissue engineered human prostate microtissues reveal key role of mast cellderived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitro. Biomaterials, 197. pp. 72-85. ISSN 0142-9612

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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Files associated with this item cannot be displayed due to copyright restrictions.
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Date Deposited: 03 Oct 2019 07:26
Last Modified: 20 Nov 2019 05:29
Uncontrolled Keywords: prostate cancer; cancer-associated fibroblasts; melt electrowritten scaffolds; tumour microenvironment; mast cells 3D model
Fields of Research : 11 Medical and Health Sciences > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology
06 Biological Sciences > 0601 Biochemistry and Cell Biology > 060106 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
09 Engineering > 0903 Biomedical Engineering > 090301 Biomaterials
Socio-Economic Objective: C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders
Identification Number or DOI: 10.1016/j.biomaterials.2018.12.030
URI: http://eprints.usq.edu.au/id/eprint/35436

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