PESO: Breast Cancer Invasion in Crowded and Locally Stiff Environments

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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.