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Review Open Access

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

  • Authors:
    • Guangjie Zhang
    • Qindong Liang
    • Yongfang Wu
    • Yingshuang Wang
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, Chengdu Fifth People's Hospital (The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan 611130, P.R. China, Clinical Laboratory Center, The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, Gansu 730030, P.R. China, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 185
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    Published online on: September 4, 2025
       https://doi.org/10.3892/ijmm.2025.5626
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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.
View Figures

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.
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Spandidos Publications style
Zhang G, Liang Q, Wu Y and Wang Y: Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review). Int J Mol Med 56: 185, 2025.
APA
Zhang, G., Liang, Q., Wu, Y., & Wang, Y. (2025). Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review). International Journal of Molecular Medicine, 56, 185. https://doi.org/10.3892/ijmm.2025.5626
MLA
Zhang, G., Liang, Q., Wu, Y., Wang, Y."Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review)". International Journal of Molecular Medicine 56.5 (2025): 185.
Chicago
Zhang, G., Liang, Q., Wu, Y., Wang, Y."Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 185. https://doi.org/10.3892/ijmm.2025.5626
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang G, Liang Q, Wu Y and Wang Y: Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review). Int J Mol Med 56: 185, 2025.
APA
Zhang, G., Liang, Q., Wu, Y., & Wang, Y. (2025). Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review). International Journal of Molecular Medicine, 56, 185. https://doi.org/10.3892/ijmm.2025.5626
MLA
Zhang, G., Liang, Q., Wu, Y., Wang, Y."Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review)". International Journal of Molecular Medicine 56.5 (2025): 185.
Chicago
Zhang, G., Liang, Q., Wu, Y., Wang, Y."Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 185. https://doi.org/10.3892/ijmm.2025.5626
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