期刊
BIOMATERIALS
卷 197, 期 -, 页码 72-85出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.12.030
关键词
Prostate cancer; Cancer-associated fibroblasts; Melt electrowritten scaffolds; Tumour microenvironment; Mast cells; 3D model
资金
- National Health and Medical Research Council of Australia [1102752, 1106870]
- Victorian Government through the Victorian Cancer Agency [MCRF15023, MCRF18017]
- Australian Government Research Training Program (RTP) Scholarship
- Australian Research Council (ITTC in Additive Biomanufacturing)
- Science and Engineering Faculty, QUT
- National Health and Medical Research Council of Australia [1106870] Funding Source: NHMRC
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 micro environmental drivers of prostate cancer progression.
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