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

虽然在与癌症的斗争中取得了重大进展，这主要是由于诊断技术和治疗方法的大幅改进，但治疗在对抗那些已经扩散到其他器官或转移的肿瘤方面的效果要差得多。 癌细胞的特定亚群，称为癌症干细胞，可能主要负责建立这些转移性集落，但确切的机制是未知的，在很大程度上是由于缺乏癌症干细胞的通用分子定义，通过这些细胞可以分离和研究。对于这个研究项目，研究小组假设癌症干细胞具有固有的流变学和粘弹性，有利于转移性侵袭和生长，这些机械特性可用于特异性识别癌症干细胞，以补充分子表型。 该团队将通过进行旨在（1）确定细胞机械特性与CD 44 +/CD 24-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CD 44 +/CD 24-乳腺癌干细胞表型之间的调节串扰的研究来验证这一假设。 智力优势： 这项研究旨在解决物理科学和肿瘤学界面的复杂问题。 因此，化学工程，生物物理学和医学科学的原理和技术将被用来实现研究目标。 该项目中的变革性研究和新方法将最终揭示调节癌症干细胞机械特性的分子途径，这是迄今为止科学界尚未解决的主题。 更广泛的影响：该项目将多学科研究与教育相结合，将对工程和生命科学、下一代生物工程研究人员的培训、生物技术开发和公共卫生产生更广泛的影响。 PI和co-PI将通过经验指导参与该研究项目的学生，使他们能够提高自己的科学知识，并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高级学位。该项目还将对社会和公共卫生产生重大影响，因为研究结果可用于开发诊断，免疫学和治疗方法，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.