It is now well established that the tumor microenvironment plays a key role in determining cancer growth, metastasis and drug resistance. Thus, it is fundamental to understand how cancer cells interact and communicate with their stroma and how this crosstalk regulates disease initiation and progression. In this setting, 3D cell cultures have gained a lot of interest in the last two decades, due to their ability to better recapitulate the complexity of tumor microenvironment and therefore to bridge the gap between 2D monolayers and animal models. Herein, we present an overview of the 3D systems commonly used for studying tumor–stroma interactions, with a focus on recent advances in cancer modeling and drug discovery and testing.

Epithelial-to-mesenchymal transition (EMT) is a step-wise process observed in normal and tumor cells leading to a switch from epithelial to mesenchymal phenotype. In tumors, EMT provides cancer cells with a metastatic phenotype characterized by E-cadherin down-regulation, cytoskeleton reorganization, motile and invasive potential. E-cadherin down-regulation is known as a key event during EMT. However, E-cadherin expression can be influenced by the different experimental settings and environmental stimuli so that the paradigm of EMT based on the loss of E-cadherin determining tumor cell behavior and fate often becomes an open question. In this review, we aimed at focusing on some critical points in order to improve the knowledge of the dynamic role of epithelial cells plasticity in EMT and, specifically, address the role of E-cadherin as a marker for the EMT axis.

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.

Three-dimensional (3D) cell cultures allow the mimic of functions of living tissues and provide key information encoded in tissue architecture. Considered the pivotal role of epithelial-to-mesenchymal transition (EMT) in carcinoma progression, including prostate cancer (PCa), we aimed at investigating the effect of the 3D arrangement on the expression of some key markers of EMT in cultured human prostate cancer (PCa) cells, to better understand PCa cell behavior. PC3 and DU145 PCa cells were cultured in RPMI cell culture medium either in 2D-monolayers or in 3D-spheroids. The main EMT markers E-cadherin, N-cadherin, α-smooth muscle actin (αSMA), vimentin, Snail, Slug, Twist and Zeb1 were evaluated by confocal microscopy, real-time PCR and Western blot. Confocal microscopy revealed that E-cadherin was similarly expressed at the cell boundaries on the plasma membrane of PCa cells grown in 2D-monolayers, as well as in 3D-spheroids, but resulted up-regulated in 3D-spheroids, compared to 2D-monolayers, at the mRNA and protein level. Moreover, markers of the mesenchymal phenotype were expressed at very low levels in 3D-spheroids, suggesting important differences in the phenotype of PCa cells grown in 3D-spheroids or in 2D-monolayers. Considered as a whole, our findings contribute to a clarification of the role of EMT in PCa and confirm that a 3D cell culture model could provide deeper insight into the understanding of the biology of PCa.

Sperm protein 17 (Sp17) is a highly conserved mammalian protein characterized in rabbit, mouse, monkey, baboon, macaque, human testis and spermatozoa. mRNA encoding Sp17 has been detected in a range of murine and human somatic tissues. It was also recognized in two myeloma cell lines and in neoplastic cells from patients with multiple myeloma and ovarian carcinoma. These data all indicate that Sp17 is widely distributed in humans, expressed not only in germinal cells and in a variety of somatic tissues, but also in neoplastic cells of unrelated origin.