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Biophysical Benchmarks of Malignancy in Primary Breast Tumor Cells

原发性乳腺肿瘤细胞恶性肿瘤的生物物理基准

基本信息

批准号：
310946797
负责人：
Professor Dr. Ben Fabry
金额：
--
依托单位：
Frauenklinik
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/310946797?language=en
关键词：
Biophysical Benchmarks Malignancy Primary Breast

项目摘要

The process of cancer cell invasion in tissue is poorly understood due to a lack of mechanistic knowledge of underlying physical principles and limited physiological relevance of 3-dimensional (3D) invasion test systems. This proposal will systematically test the hypothesis of a mechanistic link between mechanical properties of primary breast tumor cells and their metastatic potential. Comparing primary patient-derived tumor and normal breast cells in 2D and 3D environments, we will determine the stiffness, shape, protrusion dynamics, mechanotransduction and traction forces of migrating cells. Moreover, we will explore the statistical properties of cell migration and invasion, using a variety of differently stiff, porous and adhesive natural extracellular matrices. Current in vitro extracellular matrix models often give contradictory results and are far from replicating the physiological situation in vivo. Therefore, we will develop 3D cell culture systems with tunable and precisely controllable parameters that will allow us to monitor the invasion of primary breast cancer cells with high-resolution imaging and novel high-throughput methods. We predict significant differences in the biomechanical properties and the invasion behavior between primary tumor cells that have metastasized versus those that have not. These in vitro predictions will be correlated with in vivo clinical findings from the same patient cohort.

由于缺乏基本物理原理的机械知识和三维（3D）侵入测试系统的有限生理相关性，对癌细胞侵入组织的过程了解甚少。该提案将系统地测试原发性乳腺肿瘤细胞的机械性质与其转移潜力之间的机械联系的假设。在2D和3D环境中比较原发性患者来源的肿瘤和正常乳腺细胞，我们将确定迁移细胞的刚度，形状，突出动力学，机械转导和牵引力。此外，我们将探索细胞迁移和侵袭的统计特性，使用各种不同的刚性，多孔性和粘性的天然细胞外基质。目前的体外细胞外基质模型经常给出矛盾的结果，并且远不能复制体内的生理情况。因此，我们将开发具有可调和精确可控参数的3D细胞培养系统，使我们能够通过高分辨率成像和新型高通量方法监测原发性乳腺癌细胞的侵袭。我们预测在生物力学性质和侵袭行为之间的主要肿瘤细胞，已经转移与那些没有的显着差异。这些体外预测将与同一患者队列的体内临床结果相关。