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. 2013 Jul;34(20):4777-85.
doi: 10.1016/j.biomaterials.2013.03.005. Epub 2013 Apr 2.

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

Ashlee K Clark  1 , Anna V Taubenberger, Renea A Taylor, Birunthi Niranjan, Zhen Y Chea, Elena Zotenko, Shirly Sieh, John S Pedersen, Sam Norden, Mark Frydenberg, Jeremy P Grummet, David W Pook; Australian Prostate Cancer BioResource; Clare Stirzaker, Susan J Clark, Mitchell G Lawrence, Stuart J Ellem, Dietmar W Hutmacher, Gail P Risbridger
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A bioengineered microenvironment to quantitatively measure the tumorigenic properties of cancer-associated fibroblasts in human prostate cancer

Ashlee K Clark et al. Biomaterials. 2013 Jul.

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.

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