title: Targeting ROCK2 rather than ROCK1 inhibits Ewing sarcoma malignancy.
abstract: Understanding the molecular processes characterizing Ewing sarcoma (EWS) cell migration is crucial to highlight novel therapies for patients with disseminated disease. In this study we analyzed the role of ROCK kinases in the regulation of cell migration, growth and differentiation of EWS cells. Overexpression of ROCK promotes invasion and metastasis in many solid tumors. However, the effect of ROCK in EWS has not been extensively investigated. Expression of ROCK1 and ROCK2 was analyzed by western blotting in a representative panel of human EWS cell lines, in comparison with the parameters of in vitro malignancy. We investigated the effects of a ROCK2 specific inhibitor toward those of a pan-ROCK inhibitor on the growth, migration and differentiation of two EWS cell lines. ROCK2 but not ROCK1 expression was found to be associated with in vitro cell migration and anchorage‑independent growth capabilities. Exposure of EWS cells to ROCK inhibitors significantly reduced migration and growth, while favoring morphology changes and neural differentiation. These effects were more striking when cells were specifically deprived of ROCK2 activity. Our findings lead to consider ROCK2, rather than ROCK1, as a possible molecular target for the treatment of EWS.
authors.affiliation: CRS Development of Biomolecular Therapies, Experimental Oncology Laboratory, Rizzoli Orthopedic Institute, I-40136 Bologna, Italy.
authors.forename: Rosa Simona
authors.initials: RS
authors.lastname: Pinca
authors.affiliation: CRS Development of Biomolecular Therapies, Experimental Oncology Laboratory, Rizzoli Orthopedic Institute, I-40136 Bologna, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Manara
authors.affiliation: CRS Development of Biomolecular Therapies, Experimental Oncology Laboratory, Rizzoli Orthopedic Institute, I-40136 Bologna, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Chiadini
authors.affiliation: CRS Development of Biomolecular Therapies, Experimental Oncology Laboratory, Rizzoli Orthopedic Institute, I-40136 Bologna, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, I-40126 Bologna, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Zucchini
authors.affiliation: CRS Development of Biomolecular Therapies, Experimental Oncology Laboratory, Rizzoli Orthopedic Institute, I-40136 Bologna, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Scotlandi
mesh_terms: D000577:Amides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D011725:Pyridines / Q000494:pharmacology*; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D011725:Pyridines; C108830:Y 27632; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases