Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha, Qatar.
Biomedical Research Center (BRC), Qatar University, Doha, Qatar.
Pharm Dev Technol. 2021 Apr;26(4):490-500. doi: 10.1080/10837450.2021.1872624. Epub 2021 Feb 15.
Breast cancer is one of the leading causes of brain metastasis. Metastasis to the brain occurs if cancer cells manage to traverse the 'blood-brain barrier' (BBB), which is a barrier with a very tight junction (TJ) of endothelial cells between blood circulation and brain tissue. It is highly important to develop novel BBB models to investigate breast cancer metastasis to the brain to facilitate the screening of chemotherapeutic agents against it. We herein report the development of gelatin methacryloyl (GelMA) modified transwell insert based BBB model composed of endothelial and astrocyte cell layers for testing the efficacy of anti-metastatic agents against breast cancer metastasis to the brain. We characterized the developed model for the morphology and in vitro breast cancer cell migration. Furthermore, we investigated the effect of cisplatin, a widely used chemotherapeutic agent, on the migration of metastatic breast cancer cells using the model. Our results showed that breast cancer cells migrate across the developed BBB model. Cisplatin treatment inhibited the migration of cancer cells across the model. Findings of this study suggest that our BBB model can be used as a suitable tool to investigate breast cancer-associated brain metastasis and to identify suitable therapeutic agents against this.
乳腺癌是脑转移的主要原因之一。如果癌细胞设法穿过“血脑屏障”（BBB），就会发生脑转移，BBB 是血液循环和脑组织之间具有非常紧密连接（TJ）的内皮细胞屏障。开发新型 BBB 模型以研究乳腺癌向脑转移对于筛选针对它的化疗药物非常重要。我们在此报告了基于明胶甲基丙烯酰（GelMA）修饰的 Transwell 插入物的 BBB 模型的开发，该模型由内皮细胞和星形胶质细胞层组成，用于测试抗转移剂对乳腺癌向脑转移的疗效。我们对开发的模型的形态和体外乳腺癌细胞迁移进行了表征。此外，我们使用该模型研究了顺铂（一种广泛使用的化疗药物）对转移性乳腺癌细胞迁移的影响。我们的结果表明，乳腺癌细胞穿过了开发的 BBB 模型。顺铂处理抑制了癌细胞穿过模型的迁移。这项研究的结果表明，我们的 BBB 模型可用作研究乳腺癌相关脑转移的合适工具，并鉴定针对这种疾病的合适治疗药物。
