PMID- 21276769 OWN - NLM STAT- MEDLINE DCOM- 20110620 LR - 20211020 IS - 1096-0309 (Electronic) IS - 0003-2697 (Print) IS - 0003-2697 (Linking) VI - 412 IP - 1 DP - 2011 May 1 TI - Molecular imaging of c-Met tyrosine kinase activity. PG - 1-8 LID - 10.1016/j.ab.2011.01.028 [doi] AB - The receptor tyrosine kinase c-Met and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), modulate signaling cascades implicated in cellular proliferation, survival, migration, invasion, and angiogenesis. Therefore, dysregulation of HGF/c-Met signaling can compromise the cellular capacity to moderate these activities and can lead to tumorigenesis, metastasis, and therapeutic resistance in various human malignancies. To facilitate studies investigating HGF/c-Met receptor coupling or c-Met signaling events in real time and in living cells and animals, here we describe a genetically engineered reporter where bioluminescence can be used as a surrogate for c-Met tyrosine kinase activity. c-Met kinase activity in cultured cells and tumor xenografts was monitored quantitatively and dynamically in response to the activation or inhibition of the HGF/c-Met signaling pathway. Treatment of tumor-bearing animals with a c-Met inhibitor and the HGF neutralizing antibody stimulated the reporter's bioluminescence activity in a dose-dependent manner and led to a regression of U-87 MG tumor xenografts. Results obtained from these studies provide unique insights into the pharmacokinetics and pharmacodynamics of agents that modulate c-Met activity and validate c-Met as a target for human glioblastoma therapy. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Zhang, Limin AU - Zhang L AD - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA. FAU - Virani, Shama AU - Virani S FAU - Zhang, Yu AU - Zhang Y FAU - Bhojani, Mahaveer S AU - Bhojani MS FAU - Burgess, Teresa L AU - Burgess TL FAU - Coxon, Angela AU - Coxon A FAU - Galban, Craig J AU - Galban CJ FAU - Ross, Brian D AU - Ross BD FAU - Rehemtulla, Alnawaz AU - Rehemtulla A LA - eng GR - P50 CA093990-10/CA/NCI NIH HHS/United States GR - P01 CA085878-09/CA/NCI NIH HHS/United States GR - U24CA083099/CA/NCI NIH HHS/United States GR - U24 CA083099/CA/NCI NIH HHS/United States GR - R01 CA129623/CA/NCI NIH HHS/United States GR - U24 CA083099-10/CA/NCI NIH HHS/United States GR - R01CA129623/CA/NCI NIH HHS/United States GR - P01CA085878/CA/NCI NIH HHS/United States GR - P50CA093990/CA/NCI NIH HHS/United States GR - R01 CA129623-05/CA/NCI NIH HHS/United States GR - P01 CA085878/CA/NCI NIH HHS/United States GR - P50 CA093990/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20110127 PL - United States TA - Anal Biochem JT - Analytical biochemistry JID - 0370535 RN - 0 (Antibodies, Neutralizing) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Animals MH - Antibodies, Neutralizing/immunology MH - Cell Line, Tumor MH - Genes, Recessive MH - Glioblastoma/therapy MH - Hepatocyte Growth Factor/metabolism MH - Humans MH - Mice MH - Mice, Nude MH - Molecular Imaging/*methods MH - Proto-Oncogene Proteins c-met/*metabolism/therapeutic use MH - Signal Transduction MH - Transplantation, Heterologous PMC - PMC3265038 MID - NIHMS269035 EDAT- 2011/02/01 06:00 MHDA- 2011/06/21 06:00 PMCR- 2012/05/01 CRDT- 2011/02/01 06:00 PHST- 2010/08/31 00:00 [received] PHST- 2011/01/14 00:00 [revised] PHST- 2011/01/21 00:00 [accepted] PHST- 2011/02/01 06:00 [entrez] PHST- 2011/02/01 06:00 [pubmed] PHST- 2011/06/21 06:00 [medline] PHST- 2012/05/01 00:00 [pmc-release] AID - S0003-2697(11)00055-8 [pii] AID - 10.1016/j.ab.2011.01.028 [doi] PST - ppublish SO - Anal Biochem. 2011 May 1;412(1):1-8. doi: 10.1016/j.ab.2011.01.028. Epub 2011 Jan 27.