Targeting microtentacles on circulating breast tumor cells to reduce metastasis

World Congress on Breast Cancer

August 03-05, 2015 Birmingham, UK

Stuart S Martin, Marlene and Stewart Greenebaum

University of Maryland, USA

Posters-Accepted Abstracts: J Cancer Sci Ther

Abstract :

The great majority of current cancer drug development focuses on inhibiting tumor cell growth or local invasion. Comparatively little is known about therapeutic targets in CTCs or the effects of existing chemotherapies on CTCs.Our lab 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. Our current studies now show that McTNs are an independent marker of tumor stem cell characteristics.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 found that the common cytoskeletal drugs, such as the tubulin-stabilizing drug, Taxol, actually enhance 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. Together with engineering collaborators, we have developed a novel microfluidic medical device for imaging cytoskeletal dynamics in free-floating patient tumor cells. Using live-cell confocal microscopy, we have now demonstrated that McTNs are detectable within hours of when tumor cells are recovered from patients.This technology enables immediate testing of patient cells for responses to drugs that could influence CTC reattachment during metastasis.