The role of mechanics in tumor progression and malignancy

力学在肿瘤进展和恶性肿瘤中的作用

• 批准号: 8165998
• 负责人: Ovijit Chaudhuri
• 金额: $ 5.13万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-16 至 2013-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8165998
• 关键词: Affect; Alginates; Behavior; Breast Cancer Cell; Cell Adhesion; Cell Culture Techniques; Cell Line; Cell model; Cells; Dependence; Elasticity; Environment; Epithelial; Epithelial Cell Proliferation; Epithelial Cells; Functional disorder; Gel; Goals; Growth; Health; In Vitro; Individual; Lead; Ligands; Malignant - descriptor; Malignant Neoplasms; Mammary gland; Measurement; Measures; Mechanics; Nature; Neoplasm Metastasis; Non-Malignant; Physiological; Play; Premalignant; Property; Relative (related person); Relaxation; Role; Stress; Techniques; Testing; Tumor Cell Line; cancer cell; cancer diagnosis; density; insight; malignant phenotype; migration; reconstitution; research study; response; tumor; tumor progression; viscoelasticity

DESCRIPTION (provided by applicant): The role of mechanics in tumor progression and malignancy over the last few decades, various studies have converged upon the idea that the microenvironment is important in the progression of cancer. Specifically, the normal interactions with the microenvironment can suppress tumor formation and growth, while disruption of the normal context can support the progression and metastasis of tumors. More recent studies have suggested that the mechanical properties of the microenvironment plays an important role in this interaction, but the mechanism by which cells sense the mechanics of the environment, and how this interaction is altered in cancer remains unknown. In this project, we will investigate the effect of mechanics of the microenvironment on mammary epithelial cell proliferation, migration, and malignancy in reconstituted three dimensional alginate gel matrices. Precise control over viscoelasticity and legend density is possible with alginate gels, and a technique to precisely measure the number of bonds cells form with the gel has been established. We will probe the effect of matrix elasticity, viscoelasticity, and ligand density on proliferation and migration of the non-malignant mammary epithelial cells, and see how this response changes for pre-malignant and malignant mammary epithelial cells. Then we will develop a technique to measure strains and stresses exerted by the cells on the alginate gels, and use these measurements to elucidate the mechanism by which the cells physically probe their microenvironment. These measurements will also be conducted across cell lines with different malignant phenotypes to determine whether differences in this mechanism are correlated with different sensitivities to the microenvironment. The experiments proposed here will provide general insight into the nature of cancer malignancy as well as the mechanism by which cells sense their mechanical microenvironment. Such insight could be relevant for diagnosis of cancer malignancy, and suggest new techniques for suppressing tumor progression and malignancy.

描述（由申请人提供）：在过去的几十年中，力学在肿瘤进展和恶性肿瘤中的作用，各种研究都融合了以下观点：微环境在癌症的发展中很重要。具体而言，与微环境的正常相互作用可以抑制肿瘤的形成和生长，而正常情况的破坏可以支持肿瘤的进展和转移。最近的研究表明，微环境的机械性能在这种相互作用中起着重要作用，但是细胞感知环境力学的机制以及如何改变癌症的这种相互作用。在该项目中，我们将研究微环境力学对重构三维藻酸盐凝胶矩阵中乳腺上皮细胞增殖，迁移和恶性肿瘤的影响。使用藻酸盐凝胶可以进行精确控制粘弹性和传说密度，并且已经确定了一种准确测量与凝胶形成的键细胞数量的技术。我们将探测基质弹性，粘弹性和配体密度对非恶性乳腺上皮细胞增殖和迁移的影响，并查看这种反应如何改变恶性和恶性乳腺上皮细胞。然后，我们将开发一种测量细胞在藻酸盐凝胶上施加的菌株和应力的技术，并使用这些测量来阐明细胞物理探测其微环境的机制。这些测量还将在具有不同恶性表型的细胞系上进行，以确定该机制的差异是否与对微环境的不同敏感性相关。这里提出的实验将提供对癌症恶性肿瘤性质的一般见解，以及细胞感知其机械微环境的机制。这种洞察力可能与诊断癌症恶性肿瘤有关，并提出了抑制肿瘤进展和恶性肿瘤的新技术。