Gleevec, an Abl family inhibitor, produces a profound change in cell shape and migration

• Published in: PloS one 2013-01, Vol.8 (1), p.e52233-e52233
• Main Authors: Chen, Zaozao, Lessey, Elizabeth, Berginski, Matthew E, Cao, Li, Li, Jonathan, Trepat, Xavier, Itano, Michelle, Gomez, Shawn M, Kapustina, Maryna, Huang, Cai, Burridge, Keith, Truskey, George, Jacobson, Ken
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Adhesion; Adhesion tests; Adhesive strength; Animals; Antineoplastic Agents - pharmacology; Benzamides - pharmacology; Biology; Biomedical engineering; Biophysics; Bladder; Bladder cancer; Cancer; Cancer research; Cell adhesion; Cell adhesion & migration; Cell Adhesion - drug effects; Cell cycle; Cell migration; Cell motility; Cell Movement - drug effects; Cell Shape - drug effects; Cell size; Citologia; Collagen; Contractility; Cytology; Engineering; Enzyme inhibitors; Fluorescence; Fluorescence microscopy; Growth factors; Imatinib; Imatinib Mesylate; Influence; Inhibitors; Kinases; Laminar flow; Medicine; Microscopy; Microscopy, Interference; Morphology; Motilitat cel·lular; Myosin; Myosins - metabolism; Phenotype; Phosphorylation; Physics; Physiology; Piperazines - pharmacology; Protein kinases; Protein-tyrosine kinase; Proteïnes quinases; Proto-Oncogene Proteins c-abl - antagonists & inhibitors; Proto-Oncogene Proteins c-abl - metabolism; Pyrimidines - pharmacology; Rats; Reflection; rhoA GTP-Binding Protein - metabolism; RhoA protein; Shear Strength; Signal transduction; Stress, Mechanical; Substrates; Traction force; Tumor cells; Tumor Cells, Cultured; Urinary bladder; Urinary Bladder - drug effects; Urinary Bladder Neoplasms - drug therapy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052233

The issue of how contractility and adhesion are related to cell shape and migration pattern remains largely unresolved. In this paper we report that Gleevec (Imatinib), an Abl family kinase inhibitor, produces a profound change in the shape and migration of rat bladder tumor cells (NBTII) plated on collagen-coated substrates. Cells treated with Gleevec adopt a highly spread D-shape and migrate more rapidly with greater persistence. Accompanying this more spread state is an increase in integrin-mediated adhesion coupled with increases in the size and number of discrete adhesions. In addition, both total internal reflection fluorescence microscopy (TIRFM) and interference reflection microscopy (IRM) revealed a band of small punctate adhesions with rapid turnover near the cell leading margin. These changes led to an increase in global cell-substrate adhesion strength, as assessed by laminar flow experiments. Gleevec-treated cells have greater RhoA activity which, via myosin activation, led to an increase in the magnitude of total traction force applied to the substrate. These chemical and physical alterations upon Gleevec treatment produce the dramatic change in morphology and migration that is observed.