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Development of a highly pulmonary metastatic orthotopic renal cell carcinoma murine model

 Jee Soo Park  ;  Myung Eun Lee  ;  Seung Hwan Kim  ;  Won Sik Jang  ;  Won Sik Ham 
 BIOLOGY OPEN, Vol.10(4) : bio058566, 2021-04 
Journal Title
Issue Date
Kidney ; Lung ; Metastasis ; Mouse ; Orthotopic ; Renal cell carcinoma
The incidence of renal cell carcinoma (RCC) is high, and its outcomes remain poor. Mortality is attributable largely to metastatic disease and a dearth of effective therapeutic interventions. The lungs are the most common metastatic site. To elucidate the biological mechanisms underlying pulmonary metastasis and identify superior therapeutic strategies, we developed a novel and clinically relevant murine RCC model exhibiting enhanced pulmonary metastasis. Mice underwent intrarenal implantation using luciferase-expressing Renca, a murine renal adenocarcinoma cell line. Primary renal tumor progression and development of metastatic lung lesions were monitored in live mice using bioluminescent imaging, followed by post-mortem organ assessment. Cells were isolated from pulmonary metastases for reimplantation, followed by repeat monitoring and assessment. This process was repeated once more for a total of two in vivo passages to select for pulmonary metastatic Renca cell subpopulations. However, a single round of in vivo selection was sufficient to produce a near-maximally metastatic subpopulation. Relative to Renca cell-implanted mice, subpopulation-implanted mice exhibited shorter implantation-metastasis intervals (5 days), shorter implantation-moribundity intervals (sacrificed at 18.6±2.9 versus 22.3±1.1 days), a higher number of metastatic lung lesions at 23 days (183.9±39.0 versus 172.6±38.2) and poorer survival. Implantation of cells derived from the second round of in vivo selection produced no further significant differences in the above metrics. This model consistently and efficiently recapitulates RCC pulmonary metastasis while allowing in vivo monitoring of tumor progression, thereby facilitating elucidation of the molecular mechanisms underlying pulmonary metastasis and evaluation of therapeutic modalities.
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1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Park, Jee Soo(박지수) ORCID logo https://orcid.org/0000-0001-9976-6599
Jang, Won Sik(장원식) ORCID logo https://orcid.org/0000-0002-9082-0381
Ham, Won Sik(함원식) ORCID logo https://orcid.org/0000-0003-2246-8838
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