Animal tumors shrink when treated with anti-vascular/angiogenic (AVA) drugs, or with genetically modified cellular vectors, that cut-off their blood supplies. Clinical implementation of these promising strategies is impeded however, since the cellular factors that influence AVA are not easily measured. To help predict and monitor the AVA potential of candidate therapies, this project will develop an assay for the expression of cellular physical properties that may be involved in AVA behavior. We will focus initially on vascular-related cells, such as endothelial and other types. Several physical properties expressed by endothelial cells are suspected to influence their angiogenic potential, including: (1) adhesion to matrix; (2) cellular deformability; and (3) mechanotransduction processes. Each of these properties is mediated by specific molecules that may be useful targets of AVA therapy and can be assessed with tools that have been used and/or developed by the PI and collaborators. The proposed project will develop flow cytomechanical assay (FCMA; U.S. patent pending), a novel "front end" to standard flow cytometry, that will measure key physical properties relating to angiogenic and tumorigenic potential. During Phase I we will test the system using various cell lines, in combination with genetic manipulations and AVA drugs provided by researchers and commercial suppliers. Endpoint of the project will be proof of the FCMA concept. PROPOSED COMMERCIAL APPLICATIONS: The end product, FCMA, will be a convenient interface to standard cytometers that will be useful for researchers screening potential anti- angiogenic drugs or genetic vectors, and for clinicians to biopsy specimens. FCMA will also have general applicability to cell cytomechanics relating to several other diseases, including cardiovascular. Thus the potential market for the device is large. Patent protection currently pending will be broadened and strengthened by this project.
