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Merck
  • Utilizing human cerebral organoids to model breast cancer brain metastasis in culture.

Utilizing human cerebral organoids to model breast cancer brain metastasis in culture.

Breast cancer research : BCR (2024-07-02)
Chenran Wang, Aarti Nagayach, Harsh Patel, Lan Dao, Hui Zhu, Amanda R Wasylishen, Yanbo Fan, Ady Kendler, Ziyuan Guo
摘要

Metastasis, the spread, and growth of malignant cells at secondary sites within a patient's body, accounts for over 90% of cancer-related mortality. Breast cancer is the most common tumor type diagnosed and the leading cause of cancer lethality in women in the United States. It is estimated that 10-16% breast cancer patients will have brain metastasis. Current therapies to treat patients with breast cancer brain metastasis (BCBM) remain palliative. This is largely due to our limited understanding of the fundamental molecular and cellular mechanisms through which BCBM progresses, which represents a critical barrier for the development of efficient therapies for affected breast cancer patients. Previous research in BCBM relied on co-culture assays of tumor cells with rodent neural cells or rodent brain slice ex vivo. Given the need to overcome the obstacle for human-relevant host to study cell-cell communication in BCBM, we generated human embryonic stem cell-derived cerebral organoids to co-culture with human breast cancer cell lines. We used MDA-MB-231 and its brain metastatic derivate MDA-MB-231 Br-EGFP, other cell lines of MCF-7, HCC-1806, and SUM159PT. We leveraged this novel 3D co-culture platform to investigate the crosstalk of human breast cancer cells with neural cells in cerebral organoid. We found that MDA-MB-231 and SUM159PT breast cancer cells formed tumor colonies in human cerebral organoids. Moreover, MDA-MB-231 Br-EGFP cells showed increased capacity to invade and expand in human cerebral organoids. Our co-culture model has demonstrated a remarkable capacity to discern the brain metastatic ability of human breast cancer cells in cerebral organoids. The generation of BCBM-like structures in organoid will facilitate the study of human tumor microenvironment in culture.

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Sigma-Aldrich
抗NeuN抗体,克隆A60, clone A60, Chemicon®, from mouse
Sigma-Aldrich
抗-寡糖-2 抗体, Chemicon®, from rabbit
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抗NG2硫酸软骨素蛋白聚糖抗体, Chemicon®, from rabbit
Sigma-Aldrich
抗双皮质素抗体, serum, from guinea pig
Sigma-Aldrich
抗-SOX2 兔抗, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution