Cancer stem cell phenotyping: Establishing correlations and regulatory crosstalk between molecular markers and mechanical/rheological properties

虽然在抗击癌症方面取得了重大进展，这主要是由于诊断技术和治疗方法的大幅改进，但在对抗那些扩散到其他器官或转移的肿瘤方面，治疗方法的效果要差得多。癌细胞的特定亚群，即所谓的癌症干细胞，可能是建立这些转移克隆的主要原因，但确切的机制尚不清楚，这在很大程度上是因为缺乏对癌症干细胞的通用分子定义，通过这种定义可以分离和研究这些细胞。在这项研究项目中，研究小组假设癌症干细胞具有促进转移侵袭和生长的固有流变学和粘弹性性质，这些力学性质可用于特异性识别癌症干细胞，以补充分子表型。该团队将通过进行以下研究来验证这一假设：(1)确定细胞机械特性与CD44+/CD24-乳腺癌干细胞表型之间的相关性，以及(2)确定细胞机械特性与CD44+/CD24-乳腺癌干细胞表型之间的调节串扰。智力价值：这项研究试图解决物理科学和肿瘤学之间的复杂问题。因此，将利用化学工程、生物物理学和医学科学的原理和技术来实现研究目标。该项目中的变革性研究和新颖的方法最终将揭示调控癌症干细胞机械性能的分子途径，这是科学界迄今尚未解决的主题。更广泛的影响：该项目将多学科研究与教育相结合，并将对工程学和生命科学、培训下一代生物工程研究人员、生物技术开发和公共卫生产生更广泛的影响。PI和共同PI将通过经验指导参与这一研究项目的学生，使他们能够增进自己的科学知识，为更广泛的科学机构做出贡献，在工程或生物领域获得就业机会，或在这些学科中攻读更高的学位。该项目还将对社会和公共健康产生重大影响，因为研究成果可用于开发诊断、预后和治疗方法，以更具体地针对致命的乳腺癌干细胞。

While significant progress has been made in the fight against cancer largely due to drastic improvements in diagnostic techniques and treatment methods, therapies have been much less effective in combating those tumors that have spread to other organs, or metastasized. Specific subsets of cancer cells, known as cancer stem cells, may be primarily responsible for establishing these metastatic colonies, but the exact mechanisms are unknown, in no small part due to a lack of a universal molecular definition for cancer stem cells, through which these cells can be isolated and studied. For this research project, the research team hypothesizes that cancer stem cells possess inherent rheological and viscoelastic properties that facilitate metastatic invasion and growth, and that these mechanical properties may be used to specifically identify cancer stem cells in complement to the molecular phenotype. The team will test this hypothesis by conducting studies that aim (1) to determine correlations between cellular mechanical properties and the CD44+/CD24- breast cancer stem cell phenotype, and (2) to identify regulatory crosstalk between cellular mechanical properties and the CD44+/CD24- breast cancer stem cell phenotype. Intellectual Merit: This research seeks to address complex issues at the interface of the physical sciences and oncology. Therefore, principles and techniques from chemical engineering, biophysics, and medical sciences will be employed to achieve the study goals. The transformative studies and novel methodologies in this project will ultimately reveal molecular pathways regulating mechanical properties of cancer stem cells, subject matter that remains unaddressed by the scientific community to date. Broader impacts: This project integrates multidisciplinary research with education and will have broader impacts on engineering and the life sciences, training of the next generation of bioengineering researchers, biotechnology development, and public health. The PI and co-PIs will mentor students participating in this research project through experiences that allow them to advance their own scientific knowledge as well as contribute to the wider scientific body, gain employment in engineering or biological fields, or pursue advanced degrees in these disciplines. This project will also have a significant impact on society and public health, as the research findings can be used to develop diagnostics, prognostics, and therapeutics to more specifically target deadly breast cancer stem cells.