Abstract 1297: Novel mouse models to study bone and brain metastasis

Abstract Metastasis refers to the dissemination of cancer cells from the primary (original) tumor to distant areas of the body, where they give rise to secondary and more aggressive cancers. This process constitutes a crucial aspect of cancer progression and is frequently linked with poor prognosis. Many cancer patients progress to metastasis at a later stage of tumor development before proper treatment is available. Hence, inhibiting metastasis is an important focus of cancer research. Common tissues where cancer metastasizes include the lung, liver, bone, and brain. Anti-metastatic drugs consist of antibody drugs, small molecule inhibitors, peptides and nucleic acids. According to the different mechanisms of action, they can be categorized into angiogenic factor inhibitors, cell adhesion molecule antagonists, metalloproteinase inhibitors, cellular messenger regulators and so on. Despite significant progress in the therapeutic strategy for treating cancer metastasis, several limitations such as drug resistance and limited druggable pathways remain unsolved. To better understand the underlying mechanism and support the discovery of novel biomarkers in cancer metastasis, we have developed robust mouse models for bone and brain metastasis. MDA-MB-231-Luc cell line was injected into the left ventricle of the mouse heart using an ultrasound-guided intracardiac injection technique. Through multiple rounds of in vivo and in vitro screening, we have successfully obtained MDA-MB-231-Luc subclone cell line, which can be colonized in the spine and lower limb bones, recapitulating bone metastasis in clinic. In another approach, we have successfully established a brain metastasis model by injecting the lung cancer cell line LLC1-Luc into the common carotid artery of mice via carotid artery injection. In vivo imaging analysis confirmed cancer cells colonization and proliferation in the correspondence tissue. In conclusion, we have developed preclinical mouse models which recapitulated bone and brain metastasis observed for cancer patients in clinics. Those models can be valuable tools to study metastasis mechanisms as well as for the biomarker discovery. Citation Format: Hongyan Sun, Xue Wu, Fang Zhu, Jianming Xu, Xiang Gao, Jun Wang. Novel mouse models to study bone and brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1297.