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Abstract 2850: Astrocyte-breast cancer interactions facilitate brain metastasis

Diagnosis and treatment of breast cancer patients have been considerably improved, including those at the metastatic stage. However, brain metastasis still presents a major clinical challenge, and it is a leading cause of death. Unfortunately, there are no targeted therapies specific for this secondary tumor, and the current treatment modalities present limited clinical outcomes. Thus, better understanding of the pathways involved in the metastatic cascade, which lead to brain metastases colonization and progression, is essential. To that end, we investigated the mutual effects of astrocytes and breast cancer cells, using the traditional 2-dimensional (2D) cell-culture and a newly-established 3-dimensional (3D) model of multicellular breast cancer brain metastases spheroids. We found that astrocytes enhance the proliferation, migration and invasion of breast cancer cells, suggesting a supportive role for astrocytes in the metastatic process of breast cancer in the brain. Using a protein array, we identified several cytokines which were elevated following the co-culturing of breast cancer cells with astrocytes, suggesting them as potential key candidates involved in breast cancer-brain stroma interactions. One of these cytokines was MCP-1, which is a chemokine that is associated with poor prognosis in breast cancer patients. When it was functionally neutralized, breast cancer cell proliferation and migration rates were decreased, in addition to reduced invasion shown in our 3D-spheroid model. Considering these results, MCP-1 is proposed as one of the key factors promoting breast cancer brain metastasis. Although further validation using in vivo models is still required, this study deepens our understanding of the contribution of the metastatic breast cancer cells-brain microenvironment crosstalk to brain colonization. Taken together, our findings may be utilized to provide a novel therapeutic approach for the prevention of breast cancer brain metastasis following resection of the primary lesion. Keywords: Breast Cancer, Brain Metastasis, Brain Microenvironment, Astrocytes, Cytokines, Chemokines, MCP-1, CCL2, 3D Tumor Spheroids. Citation Format: Sahar Israeli Dangoor, Ori Hadad, Ronit Satchi-Fainaro. Astrocyte-breast cancer interactions facilitate brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2850.