Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Lab Chip. 2019 Mar 27;19(7):1162-1173. doi: 10.1039/c8lc01387j.
Brain metastases are the most lethal complication of advanced cancer; therefore, it is critical to identify when a tumor has the potential to metastasize to the brain. There are currently no interventions that shed light on the potential of primary tumors to metastasize to the brain. We constructed and tested a platform to quantitatively profile the dynamic phenotypes of cancer cells from aggressive triple negative breast cancer cell lines and patient derived xenografts (PDXs), generated from a primary tumor and brain metastases from tumors of diverse organs of origin. Combining an advanced live cell imaging algorithm and artificial intelligence, we profile cancer cell extravasation within a microfluidic blood-brain niche (μBBN) chip, to detect the minute differences between cells with brain metastatic potential and those without with a PPV of 0.91 in the context of this study. The results show remarkably sharp and reproducible distinction between cells that do and those which do not metastasize inside of the device.
脑转移是晚期癌症最致命的并发症;因此,识别肿瘤是否有可能转移到大脑是至关重要的。目前没有任何干预措施可以揭示原发性肿瘤转移到大脑的潜力。我们构建并测试了一个平台,以定量分析来自侵袭性三阴性乳腺癌细胞系和源自不同起源器官的原发性肿瘤和脑转移的患者来源异种移植物(PDX)的癌细胞的动态表型。通过结合先进的活细胞成像算法和人工智能,我们在微流控血脑腔隙(μBBN)芯片中对癌细胞的血脑外渗进行了分析,以检测具有脑转移潜力的细胞与不具有脑转移潜力的细胞之间的细微差异,在本研究中其阳性预测值为 0.91。结果表明,在设备内部转移的细胞和不转移的细胞之间存在显著而可重复的差异。