Murphy Katherine A, James Britnie R, Wilber Andrew, Griffith Thomas S
Department of Urology, University of Minnesota; Masonic Cancer Center, University of Minnesota.
Department of Urology, University of Minnesota; Masonic Cancer Center, University of Minnesota; Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota.
J Vis Exp. 2017 Apr 12(122):55080. doi: 10.3791/55080.
Renal cell carcinoma (RCC) affects > 60,000 people in the United States annually, and ~ 30% of RCC patients have multiple metastases at the time of diagnosis. Metastatic RCC (mRCC) is incurable, with a median survival time of only 18 months. Immune-based interventions (e.g., interferon (IFN) and interleukin (IL)-2) induce durable responses in a fraction of mRCC patients, and multikinase inhibitors (e.g., sunitinib or sorafenib) or anti-VEGF receptor monoclonal antibodies (mAb) are largely palliative, as complete remissions are rare. Such shortcomings in current therapies for mRCC patients provide the rationale for the development of novel treatment protocols. A key component in the preclinical testing of new therapies for mRCC is a suitable animal model. Beneficial features that recapitulate the human condition include a primary renal tumor, renal tumor metastases, and an intact immune system to investigate any therapy-driven immune effector responses and the formation of tumor-induced immunosuppressive factors. This report describes an orthotopic mRCC mouse model that has all of these features. We describe an 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).
在美国，每年有超过6万人受肾细胞癌（RCC）影响，且约30%的RCC患者在确诊时已有多处转移。转移性肾细胞癌（mRCC）无法治愈，中位生存时间仅为18个月。基于免疫的干预措施（如干扰素（IFN）和白细胞介素（IL）-2）可使部分mRCC患者产生持久反应，而多激酶抑制剂（如舒尼替尼或索拉非尼）或抗血管内皮生长因子受体单克隆抗体（mAb）大多只能起到姑息作用，因为完全缓解的情况很少见。mRCC患者当前治疗方法的这些缺点为开发新的治疗方案提供了依据。mRCC新疗法临床前测试的一个关键组成部分是合适的动物模型。能够重现人类病情的有益特征包括原发性肾肿瘤、肾肿瘤转移以及完整的免疫系统，以研究任何治疗驱动的免疫效应反应和肿瘤诱导的免疫抑制因子的形成。本报告描述了一种具有所有这些特征的原位mRCC小鼠模型。我们描述了一种使用小鼠肾腺癌细胞系Renca的肾内植入技术，随后评估肾脏（原发部位）和肺部（转移部位）的肿瘤生长情况。
