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), 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

Research output: Contribution to journalArticleResearchpeer-review

39 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)72-85
Number of pages14
Publication statusPublished - 1 Mar 2019


  • 3D model
  • Cancer-associated fibroblasts
  • Mast cells
  • Melt electrowritten scaffolds
  • Prostate cancer
  • Tumour microenvironment

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