Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review)

Traditional cancer research generally utilizes commercial immortalized cancer cell lines cultivated in two‑dimensional (2D) culture systems. However, as cell‑cell/cell‑matrix interactions and the microenvironment cannot be explored in vivo, 2D cell culture models inadequately replicate the phenotype and physiology of original tissues. Therefore, three‑dimensional (3D) cell culture technologies, such as organoids, which present potential for mimicking the features of primary solid tumors in vivo, may be useful in cancer research. By embedding them into special medium, cancer cell lines can be propagated to form tumor organoids. Notably, cells in tumor organoids are different from their original 2D counterparts. During organoid or spheroid formation, crucial aspects including cancer biology, transcriptome, proteome, signal pathways and drug sensitivity, undergo alterations. The present review summarizes the disparities between 2D cancer cells culture and 3D tumor organoids or spheroids with the aim to guide researchers in selecting optimal models for scientific investigations.