March 2nd - Seminar - Bonnie L. King, Ph.D.
Department of Physiology
Thursday March 2nd, 2017
1425 Biomedical Physical Science
"Modeling the breast cancer-to-bone metastatic niche"
Bonnie L. King, Ph.D.
Instructor, Department of Pediatrics
Molecular Image Program
Dr. C. Lee Cox
Dr. King’s research program is dedicated to the development of strategies to prevent and treat metastatic breast cancer, which is responsible for most breast cancer mortality. The most frequent site of breast cancer metastasis is bone, and we have developed a human bone tissue explant model platform to: 1) study the biology of breast cancer cell colonization of the bone metastatic niche, and 2) evaluate therapeutic strategies within the human bone microenvironment. Using bone tissues discarded from hip replacement surgeries, we have adapted a suite of technologies to monitor dynamic breast cancer cell behaviors, including migration, colonization and proliferation, within the native 3-dimensional bone tissue microenvironment during co-culture. Most recently we have discovered that treatment of bone tissue fragments with aromatase inhibitors reduces estrogen receptor-positive (ER+) breast cancer cell proliferation, suggesting that local estrogen production in the bone microenvironment sustains ER+ breast cancer cells. Most breast cancers are ER+, and treatment with endocrine therapies has been widely successful in the prevention and treatment of this clinical subtype. However, de novo and acquired resistance to these therapies occurs in a significant number of women, and circumventing this challenge is central to achieving lasting responses. Our model offers the opportunity to study and target the local cross talk fueling progression and endocrine resistance within the microenvironment of human bone tissue.