Microassay Systems for Diagnosis of Cancer Cell Motility and Metastasis

描述(申请人提供)：癌细胞的移动性是转移的一个标志--即一个复杂的、多阶段的过程，在这个过程中，这些细胞获得组织侵袭性、定向移动性表型，从原发肿瘤中分离出来，迁移到遥远的部位，并在它们身上定居，开始新的疾病部位。尽管转移是癌症患者死亡的主要原因，但目前还没有获得批准的针对侵袭细胞运动的药物，只有少数先导化合物正在进行I期或II期临床试验。在缺乏有效药物的情况下，早期发现/诊断转移成为正在进行的抗癌斗争的关键因素。这项应用旨在开发一种概念上新颖的技术平台，用于将癌细胞的运动性和/或细胞骨架动力学与其转移潜力相关联。具体地说，将利用微纳技术、表面化学以及细胞和癌症生物学的组合来制备材料和系统，利用这些材料和系统可以(I)创建具有所需形状的微图案化的“设计”细胞群体，以及(Ii)诱导特定的细胞表型。微图案将被用来探测和区分转移性和非转移性癌细胞，基于它们极化和/或重新排列细胞骨架组织/动力学的不同能力，以响应所应用的几何形状。然后，对设计细胞数量的统计将提供对细胞侵袭性的分析测量。这样开发的分析方法将用来自细胞系的细胞和来自癌症患者的细胞进行测试。将分析方法与微流控技术相结合，可以在一个微图案化的“芯片”上筛选多个样品/物质。预计拟议的系统将比现有的侵袭性测量方法更稳健和准确，例如循环细胞计数或mRNA表达微阵列。这项工作的长期目标是将这项技术从概念验证实验发展到临床应用，在那里它将有助于拯救癌症患者的生命。

DESCRIPTION (provided by applicant): Motility of cancer cells is a hallmark of metastasis - that is, a complex, multistage process, in which these cells acquire a tissue-invasive, directional motility phenotype, detach from primary tumors, migrate to distant sites, and colonize them to start new loci of disease. Although metastasis is the major cause of mortality in cancer patients, there are currently no approved drugs available that target motility of invasive cells, and only a handful of lead compounds are being tested in Phase I or II clinical trials. In the absence of effective drugs, early detection/diagnosis of metastasis becomes a critical element in the ongoing battle against cancer. This application aims to develop a conceptually novel technological platform with which to correlate motility and/or cytoskeletal dynamics of cancer cells to their metastatic potentials. Specifically, a combination of micro/nanotechnology, surface chemistry and cell and cancer biology will be used to prepare materials and systems with which to (i) create populations of micropatterned, "designer" cells of desired shapes and (ii) elicit specific cell phenotypes. The micropatterns will be used to probe and distinguish metastatic from non-metastatic cancer cells based on their differential abilities to polarize and/or to rearrange cytoskeletal organization/dynamics in response to the applied geometries. Statistics over populations of designer cells will then provide analytical measures of the cells' invasiveness. The assays thus developed will be tested with cells from cell lines as well as those from cancer patients. Multiplexing the assays with microfluidics will allow for screening many samples/substances on one micropatterned "chip". It is expected that the proposed systems will be more robust and accurate than the existing measures of invasiveness, such as counts of circulating cells or mRNA expression microarrays. The long term goal of this work is to develop the technology from the proof-of-concept experiments to clinical applications, where it would help save lives of cancer patients.