Investig Clin Urol.  2020 Mar;61(2):216-223. 10.4111/icu.2020.61.2.216.

Establishment of patient-derived three-dimensional organoid culture in renal cell carcinoma

Affiliations
  • 1Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea. hanwk@yuhs.ac
  • 2Department of Urology, National Health Insurance Service Ilsan Hospital, Goyang, Korea.
  • 3Department of Urology, Hanyang University College of Medicine, Seoul, Korea.
  • 4Department of Urology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
  • 5Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
Renal cell carcinoma is a heterogeneous kidney cancer, and over 403,000 cases were reported worldwide in 2018. Current methods for studying renal cell carcinoma are limited to two-dimensional (2D) culture of primary cell lines and patient-derived xenograft models. Numerous studies have suggested that 2D culture poorly represents the diversity, heterogeneity, and drug-resistance of primary tumors. The time and cost associated with patient-derived xenograft models poses a realistic barrier to their clinical utility. As a biomimetic model, patient-derived three-dimensional (3D) organoid culture can overcome these disadvantages and bridge the gap between in vitro cell culture and in vivo patient-derived xenograft models. Here, we establish a patient-derived 3D organoid culture system for clear cell renal cell carcinoma and demonstrate the biomimetic characteristics of our model with respect to both primary kidney cancer and conventional 2D culture.
MATERIALS AND METHODS
Normal renal tissues and tumor tissues were collected from patients with clear cell renal cell carcinoma. The dissociated cells were cultured as conventional 2D culture and 3D organoid culture. The biomimetic characteristic of the two cultures were compared.
RESULTS
Compared with 2D culture, the 3D organoid cultures retained the characteristic lipid-rich, clear cell morphology of clear cell renal cell carcinoma. Carbonic anhydrase 9 and vimentin were validated as biomarkers of renal cell carcinoma. Expression of the two validated biomarkers was more enhanced in 3D organoid culture.
CONCLUSIONS
Patient-derived 3D organoid culture retains the characteristics of renal cell carcinoma with respect to morphology and biomarker expression.

Keyword

Carcinoma, renal cell; Organoids; Precision medicine

MeSH Terms

Biomarkers
Biomimetics
Carbonic Anhydrases
Carcinoma, Renal Cell*
Cell Culture Techniques
Cell Line
Heterografts
Humans
In Vitro Techniques
Kidney Neoplasms
Organoids*
Population Characteristics
Precision Medicine
Vimentin
Biomarkers
Carbonic Anhydrases
Vimentin
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