Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center; Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center.
Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center.
J Vis Exp. 2021 Feb 4(168). doi: 10.3791/62249.
Metastatic spread to the brain is a common and devastating manifestation of many types of cancer. In the United States alone, about 200,000 patients are diagnosed with brain metastases each year. Significant progress has been made in improving survival outcomes for patients with primary breast cancer and systemic malignancies; however, the dismal prognosis for patients with clinical brain metastases highlights the urgent need to develop novel therapeutic agents and strategies against this deadly disease. The lack of suitable experimental models has been one of the major hurdles impeding advancement of our understanding of brain metastasis biology and treatment. Herein, we describe a xenograft mouse model of brain metastasis generated via tail-vein injection of an endogenously HER2-amplified cell line derived from inflammatory breast cancer (IBC), a rare and aggressive form of breast cancer. Cells were labeled with firefly luciferase and green fluorescence protein to monitor brain metastasis, and quantified metastatic burden by bioluminescence imaging, fluorescent stereomicroscopy, and histologic evaluation. Mice robustly and consistently develop brain metastases, allowing investigation of key mediators in the metastatic process and the development of preclinical testing of new treatment strategies.
转移到大脑是许多类型癌症的常见且具有破坏性的表现。仅在美国，每年就有约 20 万名患者被诊断出患有脑转移。在提高原发性乳腺癌和全身恶性肿瘤患者的生存结果方面已经取得了重大进展；然而，患有临床脑转移的患者的预后惨淡，突显了迫切需要开发针对这种致命疾病的新型治疗药物和策略。缺乏合适的实验模型是阻碍我们对脑转移生物学和治疗理解的主要障碍之一。在这里，我们描述了一种通过尾静脉注射源自炎性乳腺癌（IBC）的内源性 HER2 扩增细胞系产生的脑转移异种移植小鼠模型，IBC 是一种罕见且侵袭性的乳腺癌。细胞用萤火虫荧光素酶和绿色荧光蛋白标记，以监测脑转移，并通过生物发光成像、荧光立体显微镜和组织学评估来量化转移负担。小鼠会强烈且一致地发生脑转移，从而可以研究转移过程中的关键介质，并开发新治疗策略的临床前测试。
