Event
Bioengineering Seminar Series: Stuart Martin
Friday, April 19, 2013
11:00 a.m.-12:00 p.m.
Pepco Room, Jeong H. Kim Engineering Bldg.
Professor Ian White
ianwhite@umd.edu
Targeting the Cytoskeletal Physics of Circulating Breast Tumor Cells to Reduce Metastasis
Stuart Martin
Associate Professor
Physiology
Marlene and Stewart Greenebaum NCI Cancer Center
University of Maryland School of Medicine
Circulating tumor cells (CTCs) can invade distant tissues and lie dormant for long periods. The eventual reemergence of these disseminated cells as metastatic tumors is the major cause of cancer patient death. However, the great majority of current cancer drug development focuses on inhibiting tumor cell growth. Comparatively little is known about therapeutic targets in CTCs or the effects of existing chemotherapies on CTCs. We have recently discovered that detached and circulating breast tumor cells generate dynamic membrane microtentacles (McTNs), that arise due to an imbalance between microtubule extension and contraction of the actin cortex specifically in detached epithelial cells. The cytoskeletal mechanism supporting McTNs matches the mechanism by which CTCs bind to blood vessel walls in vivo. Since large epithelial tumor cells are crushed when pushed through narrow capillaries by blood flow, we are targeting McTNs to reduce tumor cell reattachment and increase the fragmentation of CTCs. Conversely, we have recently published that the common tubulin-stabilizing drug, Taxol actually enhances McTNs and tumor cell reattachment. Surgery and neoadjuvant chemotherapy can increase CTCs up to 1000-fold, so understanding the CTC cytoskeleton is essential to ensure that cancer drugs do not inadvertently increase metastasis while targeting cell division. Nearly 90% of human solid tumors are epithelial carcinomas, so the molecular regulators of CTC cytoskeletal physics could affect many human cancers. In collaboration with Dr. Josef Kaes at the University of Leipzig and Dr. Wolfgang Losert at the University of Maryland Department of Physics, we are using innovative laser-based optical cell stretching technology to measure the impact of specific genetic alterations on the mechanical properties of CTCs. Imaging dynamic responses in free-floating tumor cells is a significant technical challenge, but one that we are confronting together with engineering partners in academia and industry to help improve the understanding and treatment of metastatic breast cancer.
About the Speaker
Dr. Martin received his Ph.D. from the University of California, San Diego, after training as a Howard Hughes undergraduate research fellow at the University of Virginia. Dr. Martin completed a Damon Runyon postdoctoral fellowship at Harvard Medical School that combined functional genomic studies with mouse models of breast tumor metastasis, under the mentorship of Dr. Phil Leder. In 2004, Dr. Martin joined the Marlene and Stewart Greenebaum Cancer Center and the Department of Physiology at the University of Maryland School of Medicine. Dr. Martins research focuses on the cytoskeletal dynamics of circulating tumor cells and how a greater understanding of tumor cell mechanics can reveal new therapeutic opportunities and improve the effectiveness of existing cancer drugs.
