A bioengineered microenvironment to quantitatively measure the tumorigenic properties of cancer-associated fibroblasts in human prostate cancer

Ashlee Kate Clark, Anna V Taubenberger, Renea Anne Taylor, Birunthi Niranjan, Zhen Y Chea, Elena Zotenko, Shirly Sieh, John S Pedersen, Sam Norden, Mark Frydenberg, Jeremy Grummet, David William Pook, Clare Stirzaker, Susan Clark, Mitchell Graham Lawrence, Stuart John Ellem, Dietmar Hutmacher, Gail Petuna Risbridger

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38 Citations (Scopus)

Abstract

Stromal-epithelial cell interactions play an important role in cancer and the tumor stroma is regarded as a therapeutic target. In vivo xenografting is commonly used to study cellular interactions not mimicked or quantified in conventional 2D culture systems. To interrogate the effects of tumor stroma (cancer-associated fibroblasts or CAFs) on epithelia, we created a bioengineered microenvironment using human prostatic tissues. Patient-matched CAFs and non-malignant prostatic fibroblasts (NPFs) from men with moderate (Gleason 7) and aggressive (Gleason 8-9 or castrate-resistant) prostate cancer were cultured with non-tumorigenic BPH-1 epithelial cells. Changes in the morphology, motility and phenotype of BPH-1 cells in response to CAFs and NPFs were analyzed using immunofluorescence and quantitative cell morphometric analyses. The matrix protein gene expression of CAFs, with proven tumorigenicity in vivo, had a significantly different gene expression profile of matrix proteins compared to patient matched NPFs. In co-culture with CAFs (but not NPFs), BPH-1 cells had a more invasive, elongated phenotype with increased motility and a more directed pattern of cell migration. CAFs from more aggressive tumors (Gleason 8-9 or CRPC) were not quantitatively different to moderate grade CAFs. Overall, our bioengineered microenvironment provides a novel 3D in vitro platform to systematically investigate the effects of tumor stroma on prostate cancer progression.
Original languageEnglish
Pages (from-to)4777 - 4785
Number of pages9
JournalBiomaterials
Volume34
Issue number20
DOIs
Publication statusPublished - 2013

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