Project Title: Three-dimensional (3D) Model System for Studying Breast Cancer Metastasis

Project Duration: May 23 – July 29, 2016 (10 weeks), 40 hours per week

Project Mentors

• Primary Faculty Mentor:
  • Cheryl Gomillion, College of Engineering, ctgomillion@engr.uga.edu, 706-542-0918, www.gomillionlabgroup.org

• Secondary Faculty Mentor (Name, Affiliation, website and Email/Phone):

Dr. Melissa Davis, Department of Genetics, mbdavis@uga.edu, (706) 542-5014, http://research.franklin.uga.edu/davislab/content/welcome-davis-lab

• Graduate Student/PostDoc mentors (Name, Affiliation and Email/Phone):
  • Rupali Hire, College of Engineering, rupahire@uga.edu, 706-542-3623

Project Description: Breast cancer is one of the most commonly diagnosed forms of cancer in women, with a significant percentage of breast cancer deaths (~90%) attributed to the metastasis, or spread, of cancerous tumors to other parts of the body outside of the breast. It has been reported that 2 out of 3 cases of metastatic breast cancer will metastasize to the patient bones, leading to a life expectancy of only 20 months after diagnosis. Bone metastasis occurs when cells from a cancerous tumor detach from the primary tumor (in the breast), circulate through the body via lymph fluid or blood, and settle on a new tissue, in this case, bone. Knowledge of the mechanisms that cause certain tumor cells to preferentially metastasize to bone would significantly enhance the progress towards developing effective cancer therapeutics, however, the underlying mechanisms for this tumor cell spreading are not known.

The development of three-dimensional (3D) models of mammary tissue has been widely investigated in an attempt to better understand the underlying mechanisms for both normal tissue development and tumor formation. In addition, a number of 3D in vitro model systems have been developed and investigated in an effort to better understand the metastasis of breast cancer cells to bone. Many of these systems are limited since they are formed from a material with great variability in its composition, significant factors present in the surrounding tumor environment are missing, and the mechanical properties are inconsistent. Therefore, we aim to creating a 3D in vitro model system, to investigate tumor cell metastasis to bone by creating a gradient, biomaterial-based system, which can be used to evaluate the response of metastatic cancer cells to changes in the surrounding microenvironment and mechanical properties. This system will be used for studying tumor progression as well as determining the role of key factors that may regulate this process.

REU Student Role and Responsibility: Over the course of the project, the student will gain experience in biomaterial scaffold fabrication and materials characterization, specifically focused on preparing hydrogel matrices that may be used as a platform for cell studies. In addition, the student will assist with in vitro cell culture experiments to assess cancer and normal cell behavior within the matrices. The combination of these experiences will provide a comprehensive training opportunity in key areas of biomedical research.

Expected Outcome for REU student: The student’s project will serve as a preliminary assessment of the interaction between breast cancer and normal cells within fabricated hydrogel matrices, which will provide a foundation for a longer-term project focused on implementing a model system for studying cancer cell migration and invasiveness. Findings obtained from the student’s project could contribute to the development of a manuscript intended for submission to a journal such as Biomaterials, Journal of Materials Chemistry B, or Journal of Biomedical Materials Research: Part A, in addition to a conference abstract submission for presentation at a professional society meeting such as the annual meeting of the Biomedical Engineering Society.