High-throughput intracellular microrheology: a new tool for cancer research

高通量细胞内微流变学：癌症研究的新工具

• 批准号: 8079080
• 负责人: Denis Wirtz
• 金额: $ 20.11万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-08 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8079080
• 关键词: Actins; Advanced Malignant Neoplasm; Aftercare; Atomic Force Microscopy; Ballistics; Biological Assay; Biomedical Engineering; Biophysics; Body Fluids; Cancer Biology; Carcinoma; Cell Adhesion; Cell Density; Cell Line; Cell membrane; Cell-Cell Adhesion; Cells; Cellular biology; Chemicals; Chemistry; Chemotherapy-Oncologic Procedure; Clinical; Collaborations; Complement; Complex; Computers; Cultured Tumor Cells; Cytoplasm; Cytoskeleton; Detection; Development; Devices; Diagnosis; Diagnostic; Discipline of obstetrics; Disease; Disease model; Doctor of Philosophy; Early Diagnosis; Elasticity; Engineering; Epithelial Cells; Equilibrium; Etiology; Evaluation; Fluorescence Microscopy; Growth Factor; Gynecology; Harvest; Hospitals; Immunofluorescence Immunologic; Individual; Injection of therapeutic agent; Life; Liquid substance; Malignant Epithelial Cell; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Measurement; Measures; Mechanics; Medicine; Methods; Microscope; Molecular; Morbidity - disease rate; Nature; Neoplasm Metastasis; Normal Cell; Operative Surgical Procedures; Ovarian; Ovarian Carcinoma; Ovarian Serous Adenocarcinoma; Pathology; Patients; Pharmaceutical Preparations; Phenotype; Positioning Attribute; Property; Recurrence; Reproducibility; Research; Research Personnel; Resolution; Schools; Serous; Shapes; Specimen; Staging; Stretching; Students; Surface; Survival Rate; Symptoms; Testing; Therapeutic; Time; Tumor Cell Invasion; Tumor Debulking; Viscosity; Woman; Work; anticancer research; base; cancer cell; cell injury; cell motility; cellular engineering; chemotherapeutic agent; chemotherapy; density; design; high risk; immortalized cell; improved; instrument; medical schools; migration; mortality; mouse model; oncology; particle; pressure; prevent; prototype; response; tool; wound

DESCRIPTION (provided by applicant): Cancer mortality and morbidity are critically related to tumor invasion and metastasis in which the molecular mechanisms are poorly understood. Until their etiology is better revealed, attempts to develop new cancer therapeutics would remain empirical. Cell motility, which drives cancer metastasis, involves dynamic and regulated re-arrangements of the cytoskeleton. Our work and that of several other groups have shown that cytoskeleton phenotypes are typically accompanied by drastic changes in the viscoelastic properties of the cytoskeleton, which in turn modulate the ability of the cytoskeleton to generate net pushing forces at the leading edge and allow the cell to change its shape. Changes in cell mechanical properties have long been predicted to correlate with metastatic potential. However, current cell-mechanics approaches suffer from serious drawbacks - including time of measurement, lack of multiplexing, ambiguity of measurements - which prevent a direct test of this important hypothesis. The objective of this study is to: develop a highly-optimized high-throughput ballistic injection nanorheology (htBIN) technological platform to measure the micromechanical properties in cancer cells rapidly (< 30 seconds per cell) and reliably, and to assess these biophysical properties as a function of cell migration and invasion by comparing ovarian cancer cells of low and high invasive nature to normal cells, all obtained from patients at the Johns Hopkins Hospital. The proposed instrument, which is based on multiple-particle microrheology, presents key advantages over current approaches to cell mechanics. Our device will serve as a new tool for cancer research to study cell mechanics in the context of cancer cell migration and adhesion, and may ultimately serve as a diagnostic tool for patients who are at high risk for ovarian cancer, complementing more conventional biomolecular markers of cancer in a clinical setting While our proposed approach to cell mechanics is a priori applicable to detect intracellular mechanical differences in any type of cancer cells, a primary focus of this project is ovarian cancer. Ovarian cancer was selected as the disease model in this study because it represents one of the most aggressive cancers in women.

描述（由申请人提供）：癌症死亡率和发病率与肿瘤侵袭和转移密切相关，其中分子机制知之甚少。在更好地揭示其病因之前，开发新的癌症治疗方法的尝试将仍然是经验性的。驱动癌症转移的细胞运动性涉及细胞骨架的动态和受调节的重排。我们的工作和其他几个小组的工作表明，细胞骨架表型通常伴随着细胞骨架的粘弹性的急剧变化，这反过来又调节细胞骨架在前缘产生净推力的能力，并允许细胞改变其形状。细胞机械性质的变化一直被预测与转移潜力相关。然而，目前的细胞力学方法存在严重的缺点-包括测量时间，缺乏多路复用，测量模糊-这阻止了对这一重要假设的直接测试。本研究的目的是：开发高度优化的高通量弹道注射纳米流变学（htBIN）技术平台，以快速测量癌细胞的微观力学特性（< 30秒/细胞）和可靠地，并通过将低和高侵袭性的卵巢癌细胞与正常细胞进行比较来评估这些生物物理性质作为细胞迁移和侵袭的函数，都是从约翰霍普金斯医院的病人身上获得的。拟议的仪器，这是基于多粒子微观流变学，目前的方法，细胞力学的关键优势。我们的设备将作为癌症研究的新工具，在癌细胞迁移和粘附的背景下研究细胞力学，并可能最终作为卵巢癌高风险患者的诊断工具，虽然我们提出的细胞力学方法先验地适用于检测任何类型的肿瘤细胞中的细胞内力学差异，癌细胞，这个项目的主要重点是卵巢癌。卵巢癌被选为本研究中的疾病模型，因为它代表了女性中最具侵袭性的癌症之一。