PHA665752, a small-molecule inhibitor of c-Met, inhibits hepatocyte growth factor-stimulated migration and proliferation of c-Met-positive neuroblastoma cells |
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| Authors: | Hal E Crosswell Anindya Dasgupta Carlos S Alvarado Tanya Watt James G Christensen Pradip De Donald L Durden and Harry W Findley |
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| Institution: | (1) Division of Pediatric Hematology/Oncology, Children's Hospital and University Medical Group of the Greenville Hospital System, 29605 Greenville, SC, USA;(2) Division of Pediatric Hematology/Oncology and Bone Marrow Transplantation, AFLAC Cancer Center and Blood Disorders Service, Department of Pediatrics, Emory University School of Medicine, 30022 Atlanta, GA, USA;(3) Cancer Biology, Pfizer Inc., 92121 La Jolla, CA, USA |
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| Abstract: | Background c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), and both c-Met and its ligand are
expressed in a variety of tissues. C-Met/HGF/SF signaling is essential for normal embryogenesis, organogenesis, and tissue
regeneration. Abnormal c-Met/HGF/SF signaling has been demonstrated in different tumors and linked to aggressive and metastatic
tumor phenotypes. In vitro and in vivo studies have demonstrated inhibition of c-Met/HGF/SF signaling by the small-molecule inhibitor PHA665752. This study investigated
c-Met and HGF expression in two neuroblastoma (NBL) cell lines and tumor tissue from patients with NBL, as well as the effects
of PHA665752 on growth and motility of NBL cell lines. The effect of the tumor suppressor protein PTEN on migration and proliferation
of tumor cells treated with PHA665752 was also evaluated. |
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