Basic Research - Cancer(구연) (E-009)

폐전이 신세포암 마우스 모델의 개발
연세의대 신촌세브란스병원
박지수, 이명은, 장원식, 김종찬, 이승환, 나군호, 함원식
BACKGROUND: Renal cell carcinoma (RCC) most frequently metastasizes to the lungs, presenting solitary or multiple lung nodules. Otherwise surgically indicated, most patients with metastatic advanced RCC are treated with molecular target therapy. However, targeted therapies are largely palliative and complete remissions are rare, needing for the development of novel treatments. A key component in the preclinical testing of new therapies for mRCC is a suitable animal model, where highly efficient lung mRCC models are lacking.

OBJECTIVES: In this study, we have focused on developing highly efficient lung mRCC models.

MATERIALS & METHODS: We have established a new animal model of RCC metastasis to lung by intrarenal implantation technique using the mouse renal adenocarcinoma cell line Renca, followed by the assessment of tumor growth in the kidney (primary site) and lungs (metastatic site).

RESULTS: The animals developed aggressive lung metastatic lesions as well as primary kidney tumor development as monitored by bioluminescent imaging and india ink lung inflation. The mean time of pulmonary metastasis was 17 ± 3 days. Renca tumors in the kidney and lungs were validated by immunohistochemistry. To increase the lung-metastatic potential of the Rena cell, an in vivo selection was done yielding a subpopulation causing pulmonary metastasis with the mean time of 10 ± 2 days. The selected subline secreted more proangiogenic factors such as VEGF and bFGF in vitro compared to the parental cell line.

CONCLUSIONS: This models provides a reliable reproduction of the clinical situation of pulmonary metastasis of RCC, and therefore suitable for designing and evaluating more effective treatment plans for RCC lung metastasis.
keywords : mouse model, lung metastasis, renal cell carcinoma