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Updated: Jun 14, 2025
Modeling Brain Metastasis by Internal Carotid Artery Injection of Cancer Cells
Published on: August 2, 2022
A novel optimized orthotopic mouse model for brain metastasis with sustained cerebral blood circulation and
Zihao Liu1, Huisheng Song2, Zhenning Wang3
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Thoracic Surgery and Oncology, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510182, Guangdong, People's Republic of China.
Abstract:
Brain metastasis is thought to be related to the high mortality and poor prognosis of lung cancer. Despite significant advances in the treatment of primary lung cancer, the unique microenvironment of the brain renders current therapeutic strategies largely ineffective against brain metastasis. The lack of effective drugs for brain metastasis treatment is primarily due to the incomplete understanding of the mechanisms underlying its initiation and progression. Currently, our understanding of brain metastasis remains limited, primarily due to the absence of appropriate models that can realistically simulate the entire process of tumor cell detachment from the primary site, circulation through the bloodstream, and eventual colonization of the brain. Therefore, there is a pressing need to develop more suitable lung cancer brain metastasis models that can effectively replicate these critical stages of metastasis. Here, based on the traditional carotid artery injection model, we established a novel orthotopic mouse model by using a light-controlled hydrogel to repair the puncture site on the carotid artery, with sustained cerebral blood circulation and the capability of multiple delivery cancer cell to mimic lung cancer brain metastasis. The optimized orthotopic mouse model significantly reduced cerebral ischemia and improved cerebral oxygenation by 60% compared to the traditional orthotopic mouse model, enhancing post-operative survival rates. It also showed a reduction in pro-inflammatory cytokines and featured less inflammatory and more resting states of microglial and astrocyte cells. Furthermore, the optimized orthotopic mouse model markedly increased the success rate and absolute number of the metastatic clones in the brain. Additionally, the multiple delivery model based on the optimized orthotopic mouse model substantially augmented the tumor clone number and formation rates compared to single injection in the optimized orthotopic mouse model. This model overcomes previous limitations by maintaining cerebral circulation, providing a more accurate simulation of the continuous entry of tumor cells into cerebral circulation. It offers a robust platform for studying the interactions of cancer cells with the brain microenvironment and testing new therapeutic approaches.
Insights
Researchers developed a novel mouse model to better study lung cancer brain metastasis. This improved model enhances understanding of metastasis and aids in testing new therapies for brain tumors.
Area of Science:
- Oncology
- Neuroscience
- Cancer Biology
Background:
- Lung cancer brain metastasis leads to high mortality and poor prognosis.
- Current treatments are ineffective due to the brain's unique microenvironment.
- Limited understanding of metastasis mechanisms hinders effective drug development.
Purpose of the Study:
- To develop an improved orthotopic mouse model for lung cancer brain metastasis.
- To accurately simulate tumor cell detachment, circulation, and brain colonization.
- To provide a platform for studying cancer-brain interactions and testing therapies.
Main Methods:
- Established a novel orthotopic mouse model based on carotid artery injection.
- Utilized a light-controlled hydrogel to repair carotid artery puncture sites.
- Incorporated capability for multiple cancer cell deliveries to mimic continuous metastasis.
Main Results:
- The optimized model reduced cerebral ischemia and improved oxygenation by 60%.
- Observed reduced pro-inflammatory cytokines and less inflammatory microglial/astrocyte states.
- Markedly increased success rate and number of brain metastatic clones.
Conclusions:
- The novel orthotopic mouse model accurately simulates lung cancer brain metastasis.
- This model supports research into cancer-brain microenvironment interactions.
- It provides a robust platform for evaluating novel therapeutic strategies.
