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

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.

Original languageEnglish
Pages (from-to)72-85
Number of pages14
JournalBiomaterials
Volume197
DOIs
Publication statusPublished - 1 Mar 2019

Keywords

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

Cite this

Pereira, Brooke A. ; Lister, Natalie L. ; Hashimoto, Kohei ; Teng, Linda ; Flandes-Iparraguirre, Maria ; Eder, Angelina ; Sanchez-Herrero, Alvaro ; Niranjan, Birunthi ; Melbourne Urological Research Alliance (MURAL) ; Frydenberg, Mark ; Papargiris, Melissa M. ; Lawrence, Mitchell G. ; Taylor, Renea A. ; Hutmacher, Dietmar W. ; Ellem, Stuart J. ; Risbridger, Gail P. ; De-Juan-Pardo, Elena M. / Tissue engineered human prostate microtissues reveal key role of mast cell-derived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitro. In: Biomaterials. 2019 ; Vol. 197. pp. 72-85.
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title = "Tissue engineered human prostate microtissues reveal key role of mast cell-derived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitro",
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",
author = "Pereira, {Brooke A.} and Lister, {Natalie L.} and Kohei Hashimoto and Linda Teng and Maria Flandes-Iparraguirre and Angelina Eder and Alvaro Sanchez-Herrero and Birunthi Niranjan and {Melbourne Urological Research Alliance (MURAL)} and Mark Frydenberg 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.}",
year = "2019",
month = "3",
day = "1",
doi = "10.1016/j.biomaterials.2018.12.030",
language = "English",
volume = "197",
pages = "72--85",
journal = "Biomaterials",
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Pereira, BA, Lister, NL, Hashimoto, K, Teng, L, Flandes-Iparraguirre, M, Eder, A, Sanchez-Herrero, A, Niranjan, B, Melbourne Urological Research Alliance (MURAL), Frydenberg, M, Papargiris, MM, Lawrence, MG, Taylor, RA, Hutmacher, DW, Ellem, SJ, Risbridger, GP & De-Juan-Pardo, EM 2019, '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, vol. 197, pp. 72-85. https://doi.org/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. / Pereira, Brooke A.; Lister, Natalie L.; Hashimoto, Kohei; Teng, Linda; Flandes-Iparraguirre, Maria; Eder, Angelina; Sanchez-Herrero, Alvaro; Niranjan, Birunthi; Melbourne Urological Research Alliance (MURAL) ; Frydenberg, Mark; Papargiris, Melissa M.; Lawrence, Mitchell G.; Taylor, Renea A.; Hutmacher, Dietmar W.; Ellem, Stuart J.; Risbridger, Gail P.; De-Juan-Pardo, Elena M.

In: Biomaterials, Vol. 197, 01.03.2019, p. 72-85.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Tissue engineered human prostate microtissues reveal key role of mast cell-derived tryptase in potentiating cancer-associated fibroblast (CAF)-induced morphometric transition in vitro

AU - Pereira, Brooke A.

AU - Lister, Natalie L.

AU - Hashimoto, Kohei

AU - Teng, Linda

AU - Flandes-Iparraguirre, Maria

AU - Eder, Angelina

AU - Sanchez-Herrero, Alvaro

AU - Niranjan, Birunthi

AU - Melbourne Urological Research Alliance (MURAL)

AU - Frydenberg, Mark

AU - Papargiris, Melissa M.

AU - Lawrence, Mitchell G.

AU - Taylor, Renea A.

AU - Hutmacher, Dietmar W.

AU - Ellem, Stuart J.

AU - Risbridger, Gail P.

AU - De-Juan-Pardo, Elena M.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

KW - 3D model

KW - Cancer-associated fibroblasts

KW - Mast cells

KW - Melt electrowritten scaffolds

KW - Prostate cancer

KW - Tumour microenvironment

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U2 - 10.1016/j.biomaterials.2018.12.030

DO - 10.1016/j.biomaterials.2018.12.030

M3 - Article

VL - 197

SP - 72

EP - 85

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -