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Abstract: PO1853

Development of 3D Renal Cell Carcinoma Organoids and Cancer Invasion Assay

Session Information

Category: Onco-Nephrology

  • 1500 Onco-Nephrology

Authors

  • Lee, Nathan, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Cheng, Shun-Yang, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Bonventre, Joseph V., Brigham and Women's Hospital, Boston, Massachusetts, United States
Background

Recent advances in in vitro 3D culture technologies, such as organoids derived from hPSCs, have opened new avenues for development of human disease models. Modeling cancer by utilizing cancer organoids provides advantages as they maintain 3D cell-cell interactions, heterogeneity, microenvironment, and drug response of the sample they originate from. Such preclinical models are essential for more efficient translation of cancer research into novel treatment regimens for patients. 5-year survival rate at advanced stage IV RCC is less than 10%, as RCC is also notorious for resistance to chemotherapy and radiation therapy. Therefore, development of effective tools for better understanding and drug screening for RCC are needed. Kidney cancer organoids and novel assays such as cancer invasion assays can be useful tools to personalize potential therapeutics.

Methods

Primary kidney cancer cell lines were generated from patient biopsy samples. 3D kidney cancer organoids and non-cancer kidney organoids for cancer invasion assay were generated from primary kidney cancer cell lines and hPSCs, respectively, by modifications of our laboratory’s prior published kidney organoids techniques. Organoids were characterized by immunostaining. Upon maturation, organoids were added onto the non-cancer kidney organoids and incubated together for the invasion assay with or without treatment with drugs. Frozen sections and imaging were utilized to examine the cancer invasion. Kidney cancer organoids were treated with various drugs to investigate efficacy in reduction or inhibition of the invasion.

Results

RCC cancer organoids showed significantly better expression of kidney cancer markers such as KIM-1, HIF-1α, HIF-2α, and CAIX9 compared to 2D primary RCC cells. Addition of the cancer organoids to normal kidney organoids led to invasion of the cancer organoids into the normal kidney organoids within 3 days. Treatment of the cancer organoids by the receptor tyrosine kinase inhibitor, sunitinib or the histone acetyltransferase inhibitor (A-485) showed reduction in efficacy of cancer invasion.

Conclusion

Development and use of cancer invasion assay for renal cell carcinoma utilizing kidney cancer and normal kidney organoids could lead to better understanding of cancer invasion and provide the capability to screen and profile for identification of potential treatment options in renal cell carcinoma.

Funding

  • NIDDK Support