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

Abstract

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.

Keywords: 2‑dimensional cell culture; 3‑dimensional cell culture; cancer; cell line; organoid; spheroid.

Figure 1

3D tumor culture technology and applications. (A) Evolution of tumor modeling platforms. (B) In vitro tumor culture systems: Classification and applications. 3D tumor cultures are classified as scaffold-free, scaffold-based or in combination with other platforms (left). Translational applications (phenotyping, mechanisms, and therapies) (right). Figure was created by Bio Render and Power Point.

Figure 2

Differences in signal pathways and drug responses between 2D tumor culture and the 3D counterparts. Figure was created by Bio Render and Power Point.