Influences of the 3D microenvironment on cancer cell behaviour and treatment responsiveness: A recent update on lung, breast and prostate cancer models.

The majority of in vitro studies assessing cancer treatments are performed in two-dimensional (2D) monolayers and are subsequently validated in in vivo animal models. However, 2D models fail to accurately model the tumour microenvironment. Furthermore, animal models are not directly applicable to mimic the human scenario. Three-dimensional (3D) culture models may help to address the discrepancies of 2D and animal models. When cancer cells escape the primary tumour, they can invade at distant organs building secondary tumours, called metastasis. The development of metastasis leads to a dramatic decrease in the life expectancy of patients. Therefore, 3D systems to model the microenvironment of metastasis have also been developed. Several studies have demonstrated changes in cell behaviour and gene expression when cells are cultured in 3D compared to 2D and concluded a better comparability to cells in vivo. Of special importance is the effect seen in response to anti-cancer treatments as models are built primarily to serve as drug-testing platforms. This review highlights these changes between cancer cells grown in 2D and 3D models for some of the most common cancers including lung, breast and prostate tumours. In addition to models aiming to mimic the primary tumour site, the effects of 3D cell culturing in bone metastasis models are also described. STATEMENT OF SIGNIFICANCE: Most in vitro studies in cancer research are performed in 2D and are subsequently validated in in vivo animal models. However, both models possess numerous limitations: 2D models fail to accurately model the tumour microenvironment while animal models are expensive, time-consuming and can differ considerably from humans. It is accepted that the cancer microenvironment plays a critical role in the disease, thus, 3D models have been proposed as a potential solution to address the discrepancies of 2D and animal models. This review highlights changes in cell behaviour, including proliferation, gene expression and chemosensitivity, between cancer cells grown in 2D and 3D models for some of the most common cancers including lung, breast and prostate cancer as well as bone metastasis.