Biomechanical Phenotyping of Circulating Tumor Cells: A Window to Study Cancer Metastasis

循环肿瘤细胞的生物力学表型：研究癌症转移的窗口

• 批准号: 1536087
• 负责人: Jianping Fu
• 金额: $ 42万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1536087&HistoricalAwards=false
• 关键词: Biomechanical; Phenotyping; Circulating; Tumor; Cells

Blood-borne cancerous tumor cells are shed by both primary and metastatic tumors and they are thought to contribute to the spread of cancer to distant sites in the body. There is, therefore, a great interest in using a blood sample to capture and measure the properties of circulating tumor cells in order to predict the response of the tumor to therapy. Despite their importance, the current understanding of circulating tumor cells is extremely poor. This project will build a novel device that will separate these cells from the blood and rapidly measure their biological and biomechanical properties. The developed device will be useful beyond the isolation and measurement of tumor cell properties, as the other cellular components of blood could also be separated and mechanically measured using the device. The research will have broad impacts on students from different educational levels and genders and ethnicities, by exposing them to exciting challenges in science and engineering that have relevance to our society.It still remains a major challenge in understanding the biology of circulating tumor cells, and ultimately, improving the systems level understanding of blood-borne metastasis in cancer. This research will address the challenge in understanding the biological nature of circulating tumor cells by establishing a cell sorting device that can efficiently capture and isolate the circulating tumor cells without using any capture antibody. A microfluidic deformability microcytometer array will also be developed for high-throughput multiparametric single-cell biochemical and biomechanical phenotyping of live single circulating tumor cells. Experimental results from the deformability microcytometer will be further used to guide developments of a contact element / cohesive zone model and finite element simulation for quantifications of cell stiffness and expression levels of surface antigens of circulating tumor cells. The research team will further integrate the technological platforms with preclinical murine xenograft models to investigate the timing of circulating tumor cell release from primary tumors and their heterogeneity and biomechanical and biochemical properties.

原发肿瘤和转移性肿瘤都会释放血液传播的癌细胞，它们被认为是癌症扩散到身体远处的原因之一。因此，为了预测肿瘤对治疗的反应，人们对使用血液样本捕获和测量循环中的肿瘤细胞的特性非常感兴趣。尽管它们很重要，但目前对循环中的肿瘤细胞的了解极其贫乏。该项目将建造一种新的设备，将这些细胞从血液中分离出来，并快速测量它们的生物和生物力学特性。开发的设备将不仅仅用于分离和测量肿瘤细胞特性，因为血液中的其他细胞成分也可以使用该设备进行分离和机械测量。这项研究将对来自不同教育水平、性别和种族的学生产生广泛影响，使他们接触到与我们的社会相关的令人兴奋的科学和工程挑战。它仍然是理解循环肿瘤细胞生物学的主要挑战，并最终提高对癌症血液传播转移的系统水平的理解。这项研究将通过建立一种细胞分选设备来解决在了解循环肿瘤细胞生物学性质方面的挑战，该设备可以有效地捕获和分离循环中的肿瘤细胞，而不需要使用任何捕获抗体。还将开发一种微流控变形微细胞阵列，用于高通量、多参数、单细胞生化和生物力学表型的活体单个循环肿瘤细胞的表型鉴定。可变形性微细胞仪的实验结果将进一步用于指导接触单元/凝聚区模型的开发，以及用于量化细胞硬度和循环肿瘤细胞表面抗原表达水平的有限元模拟。研究小组将进一步将这些技术平台与临床前小鼠异种移植模型相结合，以研究原发肿瘤循环中肿瘤细胞释放的时间及其异质性以及生物力学和生化特性。