Abstract
In the last decade, three-dimensional (3D) cell culture technology has gained a lot of interest due to its ability to better recapitulate the in vivo organization and microenvironment of in vitro cultured cancer cells. In particular, 3D tumor models have demonstrated several different characteristics compared with traditional two-dimensional (2D) cultures and have provided an interesting link between the latter and animal experiments. Indeed, 3D cell cultures represent a useful platform for the identification of the biological features of cancer cells as well as for the screening of novel antitumor agents. The present review is aimed at summarizing the most common 3D cell culture methods and applications, with a focus on prostate cancer modeling and drug discovery.
Highlights
Prostate cancer (PCa) represents the second leading cause of tumor mortality among men in Western countries [1]
Exogenous addition of pyruvate to spheroid medium significantly reduced reactive oxygen species (ROS) generation and increased P-glycoprotein expression, which was suppressed by iodoacetate or 2-deoxy-d-glucose; these findings indicate that multidrug resistance (MDR) phenotype of PCa tumoroids is closely related to the glycolytic metabolism of cancer cells and can be abolished by glycolysis inhibitors via mechanisms that involve changes in the cellular redox state [62]
By using a direct current (DC) electrical field, Sauer et al have shown that Adenosine -triphosphate (ATP) released by 3D PCa cell cultures can activate purinergic receptors and elicit a Ca2+ wave propagating through the spheroid, stimulating tumor growth via ROS-mediated activation of c-Fos [67,68,69,70]
Summary
Prostate cancer (PCa) represents the second leading cause of tumor mortality among men in Western countries [1]. Considerable efforts have been made to identify the molecular mechanisms underlying its development and progression as well as to define novel approaches for its treatment [2,3] In this setting, besides the canonical in vitro and in vivo studies, several experiments have been conducted by exploiting new three-dimensional (3D) cell culture technologies, which provide a deeper understanding of PCa biology, and offer fundamental insights about PCa drug response in a cost/time effective and high throughput way [4]. The use of immortalized PCa cell lines to test the efficacy of new drugs in vitro or in vivo is economically advantageous, and responsible for the failure of several molecules entering clinical trials Based on these premises, an alternative, promising approach consisting of the ex vivo 3D culture of freshly excised PCa specimens, called patient-derived explants (PDEs), has been recently proposed.
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