Journal
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
Volume 28, Issue 14, Pages 1603-1616Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/09205063.2017.1338502
Keywords
Three-dimensional model; prostate cancer; hyaluronic acid; alginate; drug efficacy
Funding
- Chinese National Science Foundation [81272452, 21102020]
- Special Project on the Integration of Industry, Education and Research of Guangdong Province [2012B091100342]
- Science and Technology Program of Guangzhou [2013J4500014]
- Rutgers Cancer Institute of New Jersey [CCSG P30-CA072720 RSD]
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In vitro cell-based assays are widely applied to evaluate anti-cancer drug efficacy. However, the conventional approaches are mostly based on two-dimensional (2D) culture systems, making it difficult to recapitulate the in vivo tumor scenario because of spatial limitations. Here, we develop an in vitro three-dimensional (3D) prostate tumor model based on a hyaluronic acid (HA)-alginate hybrid hydrogel to bridge the gap between in vitro and in vivo anticancer drug evaluations. In situ encapsulation of PCa cells was achieved by mixing HA and alginate aqueous solutions in the presence of cells and then crosslinking with calcium ions. Unlike in 2D culture, cells were found to aggregate into spheroids in a 3D matrix. The expression of epithelial to mesenchyme transition (EMT) biomarkers was found to be largely enhanced, indicating an increased invasion and metastasis potential in the hydrogel matrix. A significant up-regulation of proangiogenic growth factors (IL-8, VEGF) and matrix metalloproteinases (MMPs) was observed in 3D-cultured PCa cells. The results of anti-cancer drug evaluation suggested a higher drug tolerance within the 3D tumor model compared to conventional 2D-cultured cells. Finally, we found that the drug effect within the in vitro 3D cancer model based on HA-alginate matrix exhibited better predictability for in vivo drug efficacy.
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