Vincent L. Cryns, MD
Professor, Department of Medicine
2012-2013 BCRF Project:
(made possible by generous support from The Housewares Charity Foundation)
Chief, Division of Endocrinology, Diabetes & Metabolism
University of Wisconsin
Co-Investigator: William J. Gradishar, MD FACP, Feinberg School of Medicine, Northwestern University
In 2011-12, Drs. Cryns and Gradishar have demonstrated that the cell stress protein αB-crystallin promotes brain metastasis by enhancing the adhesion of breast cancer cells to cells that make up blood vessels in the brain. This occurrence appears to facilitate penetration of the blood-brain barrier (BBB)- the biggest barrier in current therapies to treat cancers that have spread (metastasized) to the brain. The team has also demonstrated that αB-crystallin is a key regulator of breast cancer metastasis by preventing cell death that normally occurs when tumor cells detach from surrounding cells in the breast and escape into the bloodstream, an early step in metastasis. Taken together, these studies point to αB-crystallin as an important molecular regulator of metastasis in basal-like breast cancer and a promising drug target for these poor prognosis breast tumors.
In addition, basal-like tumors are a newly recognized type of breast cancer that are clinically aggressive and lack targeted therapies because they are estrogen receptor negative (ER-) and HER2 negative (HER2-). This type of tumor is collectively referred to as triple negative breast cancer. Drs. Cryns, Gradishar, and colleagues have shown that a cell stress protein called αB-crystallin contributes to the aggressive behavior of basal-like tumors in part by making them resistant to chemotherapy. More recently, these researchers have developed new in vivo models of basal-like breast cancer that metastasize from the breast to the brain and other organs. Using these in vivo models, this team has demonstrated that αB-crystallin is a key regulator of breast cancer metastasis.
During the next year of BCRF funding, Drs. Cryns, Gradishar, and their colleagues will use these existing models and develop new in vivo models to better understand the molecular mechanisms of metastasis and to evaluate new anti-metastatic therapies for basal-like tumors. One particularly exciting therapeutic strategy is the use of nanotechnology to improve drug delivery to tumors. In this way, these studies may provide novel insights into the mechanisms of breast cancer metastasis, a largely fatal stage of the disease with limited treatment options, and ultimately lead to improved therapies.
Mid-year Progress: During the current year of BCRF funding, the researchers have created a new genetic model of breast cancer in which the αB-crystallin gene is deleted to study its role in metastasis. The team has also demonstrated that αB-crystallin allows cells to survive in the setting of p53 mutation and Rb gene inactivation, two common molecular abnormalities in basal-like breast cancer. Notably, reducing the levels of αB-crystallin in basal-like breast cancer cells with p53 and Rb abnormalities makes them more sensitive to chemotherapy. These studies provide novel insights into the molecular mechanisms of basal-like breast cancer and point to αB-crystallin as a promising drug target in these poor-prognosis breast tumors.
Dr. Cryns received his bachelor's degree summa cum laude in biochemistry from Harvard, his medical degree from Harvard Medical School, and he did specialty training in endocrinology at Massachusetts General Hospital. His laboratory focuses on mechanisms of cell death. His lab was the first to report that a protein called αB-crystallin protects breast cancer cells from chemotherapy killing and elucidated the mechanism of this protection. Recently, Dr. Cryns's lab demonstrated that αB-crystallin plays an important role in an aggressive type of breast cancer (basal-like tumors) and predicts poor clinical outcomes. His research has been published in top medical journals, including the New England Journal of Medicine and the Journal of Clinical Investigation. His work has also been featured on National Public Radio's All Things Considered and highlighted in Nature, and Nature Reviews Cancer.
Dr. Cryns's research is funded by the NIH, The Breast Cancer Research Foundation, the Susan G. Komen Breast Cancer Foundation and other agencies. He has also served on numerous study sections at NIH and other agencies. Dr. Cryns is currently on the editorial board of Molecular Endocrinology. He has been the recipient of several awards, including an Outstanding Junior Faculty Award from the Avon Foundation, and he is an elected member of the American Society for Clinical Investigation.