A simple metastatic brain cancer model using human embryonic stem cell-derived cerebral organoids
A simple metastatic brain cancer model using human embryonic stem cell-derived cerebral organoids
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DOI：
10.1096/fj.202000372r
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发表时间：
2020-10-25
期刊：
影响因子：
4.8
通讯作者：
Lee, Min Young
中科院分区：
文献类型：
--
作者：
Choe, Mu Seog;Kim, Joong Sun;Lee, Min Young
每年，成千上万的人死于转移性脑癌。大多数转移性癌症研究使用2D细胞培养或动物模型，但它们有一些局限性，例如难以复制人体组织结构。本研究开发了一种简单的3D体外模型，以使用人癌细胞和人胚胎干细胞衍生的脑类器官（转移性脑癌脑类器官[MBCCO]）更好地复制脑转移。MBCCO模型成功地再现了转移性癌症过程，除了细胞-细胞相互作用之外，还包括细胞粘附、增殖和迁移。使用MBCCO模型，我们证明了肺特异性X蛋白（LUNX）在细胞增殖和迁移或侵袭中起重要作用。我们还观察到星形胶质细胞聚集周围和他们的相互作用，通过连接蛋白43在MBCCO模型中的癌细胞。我们分析了MBCCO模型是否可以用于筛选药物，通过测量吉非替尼，一个众所周知的抗癌药物的影响。我们还使用正常脑类器官（CO）检查了吉非替尼的毒性。因此，MBCCO模型是体外模拟人转移性脑癌的有力工具，也可用于药物筛选。
Every year, hundreds of thousands of people die because of metastatic brain cancer. Most metastatic cancer research uses 2D cell culture or animal models, but they have a few limitations, such as difficulty reproducing human tissue structures. This study developed a simple 3D in vitro model to better replicate brain metastasis using human cancer cells and human embryonic stem cell-derived cerebral organoids (metastatic brain cancer cerebral organoid [MBCCO]). The MBCCO model successfully reproduced metastatic cancer processes, including cell adhesion, proliferation, and migration, in addition to cell-cell interactions. Using the MBCCO model, we demonstrated that lung-specific X protein (LUNX) plays an important role in cell proliferation and migration or invasion. We also observed astrocyte accumulation around and their interaction with cancer cells through connexin 43 in the MBCCO model. We analyzed whether the MBCCO model can be used to screen drugs by measuring the effects of gefitinib, a well-known anticancer agent. We also examined the toxicity of gefitinib using normal cerebral organoids (COs). Therefore, the MBCCO model is a powerful tool for modeling human metastatic brain cancer in vitro and can also be used to screen drugs.