Coordination Funds

协调基金

• 批准号: 530849418
• 负责人: Professor Dr. Ingolf Sack
• 金额: --
• 依托单位: Klinik für Radiologie (mit dem Bereich Kinderradiologie) (CCM)
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/530849418?language=en
• 关键词: Coordination; Funds

The mechanical niche of cancer emerges from the collective behavior of cells, which is guided by their physical interactions with extracellular matrix, stromal cells and lymphatic and blood vessels. These mechanosensory signals result in unique material properties not found in inanimate matter and are closely linked to the emergent states of cancer cells in correlation with their aggressiveness and metastatic potential. Multiscale-multifrequency magnetic resonance elastography (mMRE) can quantitatively map material properties of tumors in vivo including tissue stiffness, friction, and fluidity. Here, we propose an interdisciplinary research unit for the study of cancer mechanics to unveil, for the first time, the mechano-physical cascade of carcinogenesis in vivo, to decipher the physical signals that transform dormant tumors into aggressive cancers, to mechanistically understand the properties of tumor niches that promote tumor development, invasive growth, and cancer recurrence after therapy, and to develop diagnostic imaging markers based on mMRE. Covering different length scales, we will sensitize micromechanical test methods and mMRE to disrupted tissue homeostasis, matrix remodeling, and non-equilibrium cellular interactions that collectively shape the mechanical microenvironment in which tumors grow and proliferate. We will combine state-of-the-art biotechnology approaches in organoid cultures and recellularized tissue scaffolds with animal tumor models, micromechanical test methods, metabolic modeling, and multiparametric, quantitative imaging including mMRE in tissue samples and patients to study the multiscale mechanical properties of the cancerogenic niche from microscopic to macroscopic length scales. This approach will allow us to thoroughly test our main hypothesis that in vivo mMRE i) is sensitive to solid-fluid mechanical property changes associated with tumor development, ii) is specific to collective cellular behavior underlying malignant transformation, and iii) predicts the formation of solid stress in carcinogenic niches. Our research plan evolves around three pillars that cover the micro-, meso- and macroscopic ranges of tumor properties. Each pillar combines innovative multiparametric imaging techniques including micromechanical tests and clinical mMRE as well as analyses of transcriptomics, proteomics, cell and nucleus shape and histopathology in both ex vivo specimens and in vivo tissues. We will systematically analyze and combine these multiscale data by viscoelastic modeling of the fundamental properties of cancers across entities and individual tumor stages with the perspective of advancing noninvasive diagnostic imaging by mMRE towards risk stratification of tumor development, aggressiveness, and recurrence after treatment. Ultimately, focusing on in vivo soft tissue mechanics, this research unit is going to tackle the long-standing yet unresolved question of the origin of cancer from the physics perspective.

癌症的机械利基是由细胞的集体行为出现的，细胞的集体行为是由它们与细胞外基质，基质细胞以及淋巴管和血管的物理相互作用引起的。这些机械增强信号导致在无生命物质中未发现的独特材料特性，并且与癌细胞的新兴状态与它们的侵略性和转移潜力相关。多尺度频率磁共振弹性弹性（MMRE）可以定量地绘制体内肿瘤的材料特性，包括组织刚度，摩擦和流动性。在这里，我们提出了一个跨学科研究单元，用于研究体内癌变的机械 - 物理级联，以破译体内的机械形态级联，以破译物理信号，这些信号将休眠的肿瘤转化为积极的癌症，从在MMRE上。覆盖不同的长度尺度，我们将对小机械测试方法和MMRE敏感，以破坏组织稳态，基质重塑和非平衡性细胞相互作用，这些相互作用共同塑造了肿瘤生长和增殖的机械微环境。我们将在器官培养物中的最新生物技术方法与动物肿瘤模型，微力学测试方法，代谢建模和多参数化，包括组织样品中的MMRE以及研究癌基生成量表的多确定性特性的量表niche niche fentengty的MMRE，结合了细胞肿瘤模型，微机械测试方法，代谢建模和多参数成像，包括MMRE，从微型niche niche straces cortecopopopics组合MMRE。这种方法将使我们能够彻底检验我们的主要假设，即体内MMRE i）对与肿瘤发育相关的固体流体机械性能变化敏感，ii）ii）特定于基于恶性转化的集体细胞行为，并且iiii）预测了在致癌壁细分中形成固体应力的形成。我们的研究计划围绕覆盖肿瘤特性的微型，中，中，宏观和宏观范围的三个支柱发展。每个支柱结合了创新的多参数成像技术，包括微机械测试和临床MMRE以及转录组学，蛋白质组学，细胞和细胞核形状和组织病理学的分析。我们将通过对跨实体和单个肿瘤阶段的癌症的基本特性进行粘弹性建模，系统地分析和组合这些多尺度数据，以透视MMRE通过MMRE朝着肿瘤发育，侵略性和治疗后复发性的危险分层来推进非侵入性诊断成像。最终，该研究部门专注于体内软组织力学，将从物理学的角度解决癌症起源的长期问题。