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 language | English |
|---|---|
| Pages (from-to) | 72-85 |
| Number of pages | 14 |
| Journal | Biomaterials |
| Volume | 197 |
| DOIs | |
| Publication status | Published - 1 Mar 2019 |
Keywords
- 3D model
- Cancer-associated fibroblasts
- Mast cells
- Melt electrowritten scaffolds
- Prostate cancer
- Tumour microenvironment
Cite this
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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 journal › Article › Research › peer-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
UR - http://www.scopus.com/inward/record.url?scp=85059800490&partnerID=8YFLogxK
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 -