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Learn MoreBrain metastases are the most common intracranial malignancy in adults. Lung cancer is the most common primary lesion for brain metastases, followed by breast cancer, malignant melanoma, gastrointestinal tumors, and kidney cancer. In children, leukemia and lymphoma are the most common primary tumors for brain metastases. Although a variety of treatment methods have been tried for clinical brain metastases, such as surgical resection, whole-brain radiotherapy, stereotactic radiotherapy, and chemotherapy, the results are poor and effective treatment is still lacking. Therefore, there is an urgent need to establish an ideal experimental model of brain metastases to enhance the study of its molecular mechanism and therapeutic measures.
Different types of brain metastasis models focus on different aspects of metastasis development. Alfa Cytology can prepare homologous and heterologous brain metastasis models for our customers. Homologous models, either spontaneous or induced, retain the immune function of the host and can be used to study the interaction between tumor cells and the host microenvironment. Allogenic brain metastasis models are further divided into orthotopic models and ectopic models. Ectopic models are more stable than orthotopic models and can be used for the study of therapeutic measures.
We use immunodeficient animals, such as nude mice and/or severely combined immunodeficient mice (SCID mice), to prepare ectopic brain, metastasis models. The models are usually made at 4-6 weeks of age. For the preparation of orthotopic models, normally immunocompetent animals are commonly used.
We typically use triple-negative breast cancer cell lines or cell lines that re-express enhanced green fluorescent protein (eGFP) for modeling. We screened the MDA-MB-231 parent cell line through several cycles of peripheral inoculation-brain metastasis-transgenic culture-peripheral inoculation, and then screened the breast cancer cell subline MDA-MB-231BR, which preferentially metastasized to the brain, to produce only brain metastasis after intracardiac injection in nude mice. To facilitate imaging, 231BR cells were then transfected with an eGFP, which has less impact on the biological properties of tumor cells.
We overexpressed A549 cells with the metalloproteinase ADAM9 to increase the invasiveness of tumor cells, which produced intracerebral micrometastases after injection. Available cell lines also include EBC-1, CPA-Yang1, PC-9, PC-14, A925LPE3, NCI-H187, DMS273, etc.
We used A375, A2058, RPMI8322, WM2664, and other cell lines to generate a high percentage of brain metastases.
Methods | Details |
Imaging assays | Regular imaging of brain metastases can provide information on the dynamic development of multiple lesions, and we provide imaging methods mainly for magnetic resonance imaging and combine high-resolution instruments with multimodal imaging. |
Pathobiological testing | Our methods include conventional HE staining and special staining, including modified Gomori silver ammonia and Alcian blue/PAS combination staining. |
Immunohistochemistry and immunoblotting | For molecular markers of brain tumor tissue we commonly use immunohistochemical methods to detect, for example, Ki-67 and proliferating cell nuclear antigen PCNA are widely used proliferation-related markers whose immunoreactivity correlates with tumor grade and prognosis. |
Clinical brain metastases are difficult to treat and have a poor prognosis, which continues to drive the development of animal models of brain metastases. Human-mouse heterozygous models are the most abundant models provided to customers by Alfa Cytology. We are actively exploring the use of genetic engineering techniques to introduce oncogenes or inactivate oncogenes as a new direction in the development of animal models of tumors, which will allow us to combine with traditional modeling approaches to prepare animal models of brain metastases that are more phenotypically stable, have a more defined mechanism, or are more similar to clinical situations. Please feel free to contact our staff for information on the animal models of brain metastases you need.