title: Ca2+-mediated rewiring of cell homing and fusion to VEGF sources.
abstract: Challenges of cell-based cancer therapy include effectively homing therapeutic cells to the disease site and producing a controlled response in recognition of the microenvironment. While stem cells have been intensively studied for treating cancer as they naturally home towards sites of injury, they have drawbacks due to their pluripotency. In this paper we have shown that a stable HEK293 cell line expressing VEGFR2 and CarQ (an engineered Ca2+-sensitive RhoA) can home towards a cell colony expressing VEGF. Upon VEGF binding to VEGFR2, a Ca2+signal is produced that in turn activates CarQ-mediated cell blebbing. With the addition of VSVG, these homing cells can further initiate pH-dependent fusion upon reaching the cell colony. This protein system can form the basis of engineering cells for therapeutic intervention by homing and inhibiting tumour growth by pH-dependent fusion.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S 3G9, Canada.
authors.forename: Abdullah A
authors.initials: AA
authors.lastname: Mosabbir
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario M5S 3G9, Canada; Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Circle, Toronto, Ontario M5S 3G4, Canada. Electronic address: kevin.truong@utoronto.ca.
authors.forename: Kevin
authors.initials: K
authors.lastname: Truong
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002459:Cell Fusion; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D002118:Calcium
keywords: Ca(2+); Migration; RhoA; VEGF