One in eight women in the United States will develop invasive breast cancer, with approximately 40% of patients positive for disseminated tumor cells (DTC) in the bone at time of diagnosis. However, it is not yet possible to predict whether these DTC in the bone will form overt metastasis that are more likely to be resistant to current therapies and comprised of cancer stem cells or if these DTC will remain indolent. The role of two niches, the endosteal and perivascular niches, within the bone marrow are thought to influence DTC migration and behavior. Recent studies have highlighted the role of the integrin alpha-v-beta-3 (?v?3) as a marker that is uniquely upregulated in bone metastasis compared to both the primary tumor and other soft tissue metastasis, and may be indicative of metastatic potential.
The specific aims of this project are to: 1) Develop and characterize a 3D in vitro model of bone marrow stroma that includes both the vascular niche and the endosteal niche; and, 2) Examine breast cancer cell trafficking and upregulation of ?v?3 within a specific niche. The research plan will enable the applicant to develop a new microfluidic platform, complimenting her background as a bioengineer, while enabling her to apply the technology to biologically relevant questions regarding cancer biology and metastasis with high spatial and temporal resolution. In addition, the fellowship application includes a training plan that leverages the rich research environment at Washington University in St. Louis outside of the lab to ensure the development of a broad set of skills necessary for a successful independent research career. The completion of the specific aims and training plan will provide the field with a new tool to study the first steps of metastasis and a new independent investigator prepared to address a broad range of unanswered and impactful questions that impact our understanding and treatment of cancer.
Breast cancer often metastasizes to bone and bone marrow, causing significant pain and decrease in patient quality of life. This project will focus on recreating a small portion of the bone and bone marrow within a 3D physical model system to study breast cancer cell interaction with the other cell types found in these specialized compartments.
