PESO: Breast Cancer Invasion in Crowded and Locally Stiff Environments

该PESO奖由材料研究部的生物材料项目授予哥伦比亚大学，由材料和表面工程项目（ENG/CMMI）和国家癌症研究所的物理科学-肿瘤学办公室（OPSO）共同资助。有了这个奖项，将追求体外方法来阐明乳腺癌侵袭的早期事件，并将发展对胶原蛋白I在这一过程中的作用的理解。实验将被设计来测试这样一个假设，即乳腺癌的侵袭性成功与细胞改变形状的能力比与细胞溶解结构蛋白的能力更密切相关。在美国，每年都有许多女性和男性死于乳腺癌，这些死亡归因于疾病的进展，包括肿瘤的侵袭，随后最终发生远处转移。实验将被设计来测试这一假设，即乳腺癌侵袭性的成功与细胞改变形状的能力比与细胞溶解结构蛋白的能力更密切相关。还将研究乳腺癌细胞在具有给定大小的刚性孔的胶原I环境中侵袭期间细胞形状变化和蛋白溶解的相对重要性。计划在体外实验中的环境，概括的生物化学，拓扑结构和机械性能的乳腺癌环境中的乳腺癌侵袭的承诺提供详细的了解乳腺癌的早期侵袭性事件。作为教育和推广活动的一部分，本科生和研究生以及博士后科学家将接受跨学科生物物理科学的培训，重点是现代成像技术。此外，PI还将为小学生开设讲座，由PI在当地小学进行授课，并通过网络模块由教师在远程学校进行授课。尽管乳腺癌的治疗在过去几十年中取得了显著进步，但每年仍有许多人死于这种疾病。在几乎所有的病例中，这些死亡都是在肿瘤转移到远处之前发生的。在这种转移发生之前，肿瘤侵入局部，为扩散到远处器官奠定了基础。在这项拟议的研究中，PI将使用体外模型研究乳腺癌的早期侵袭性事件，该模型捕获并控制体内乳腺癌环境的生物化学、拓扑结构和机械特性的关键方面。这项研究的结果最终将用于开发乳腺癌治疗的新策略。拟议的工作还将产生重大的教育外联影响。PI致力于培养年轻科学家和潜在的科学家。除了培养本科生和研究生以及博士后科学家外，PI还将通过拉比学者教师委员会的服务，为哥伦比亚大学的其他本科生增加研究机会。PI将通过开发适合小学生的显微镜和细胞迁移讲座来扩展她与年轻学生的互动。这些讲座将在当地一所特许小学举行，主要服务于STEM领域代表性不足的学生。讲座也将转换为基于网络的学习模块，可下载的幻灯片，讲座指南和演示视频用于课堂。

This PESO award to Columbia University by the Biomaterials program in the Division of Materials Research is cofunded by the Materials and Surface Engineering program (ENG/CMMI); and the Office of Physical Sciences-Oncology (OPSO) of the National Cancer Institute. With this award, in vitro approaches will be pursued to elucidate early events in breast cancer invasion, and will develop an understanding the role of collagen I in this process. Experiments will be designed to test the hypothesis that breast cancer's invasive success correlates more strongly with cell ability to change shape than with cell ability to dissolve structural proteins. Many women and men die of breast cancer every year in the United States, and these deaths are attributed to a progression of the disease that includes invasion of the tumor followed ultimately by distant metastasis. Experiments will be designed to test the hypothesis that breast cancer invasive success correlates more strongly with cell ability to change shape than with cell ability to dissolve structural proteins. Also will be studied the relative importance of cell shape change and protein dissolution during the breast cancer cell invasion in collagen I environments with variably stiff pores of given size. The planned in vitro experiments on breast cancer invasion in environments that recapitulate key aspects of the biochemistry, topology, and mechanical properties of the breast cancer environment hold promise for providing detailed understanding of early invasive events in breast cancer. As part of the educational and outreach activities, undergraduate and graduate students, and postdoctoral scientists will be trained in interdisciplinary biophysical sciences with a focus on modern imaging techniques. Moreover, the PI will develop lectures for elementary school students that will be presented by the PI at a local elementary school, and by teachers at distant schools through the use of web-based modules.Despite significant improvements in the treatment of breast cancer over the past decades, many people die from this disease every year. In almost all cases, these deaths are preceded by metastasis of the tumor to distant sites. Before this metastasis occurs, the tumor invades locally, setting the stage for spreading to distant organs. In this proposed research, the PI will study early invasive events in breast cancer with an in vitro model that captures and allows control of key aspects of the biochemistry, topology, and mechanical properties of the breast cancer environment in vivo. Findings from the proposed research will ultimately be used to develop new strategies in breast cancer treatment. The proposed work will also have substantial educational outreach impacts. The PI is strongly committed to educating young scientists and potential scientists. In addition to training undergraduate and graduate students, and postdoctoral scientists, the PI will work towards increasing research opportunities for additional undergraduate students at Columbia University though service on the Rabi Scholar Faculty Committee. The PI will extend her already substantial interaction with younger students by developing lectures on microscopy and cell migration that are appropriate for elementary school students. These lectures will be presented at a local charter elementary school primarily serving students underrepresented in the STEM fields. The lectures will also be converted to web-based learning modules, with downloadable slides, lecture guides, and demonstration videos for use in classrooms.