Tumor and Plasma Met Levels in Non-Metastatic Prostate Cancer
Authors: Deborah R Kaye
PLoS ONE, 2016;11(6):e0157130.
Species: Human
Sample Type: Whole Tissue
Application: ELISA Capture
A pharmacodynamic/pharmacokinetic study of ficlatuzumab in patients with advanced solid tumors and liver metastases.
Authors: Tabernero J, Elez M, Herranz M, Rico I, Prudkin L, Andreu J, Mateos J, Carreras M, Han M, Gifford J, Credi M, Yin W, Agarwal S, Komarnitsky P, Baselga J
Clin Cancer Res, 2014;20(10):2793-804.
Species: Human
Sample Type: Serum
Application: ELISA Capture
Safety, pharmacokinetics, and pharmacodynamics of AMG 102, a fully human hepatocyte growth factor-neutralizing monoclonal antibody, in a first-in-human study of patients with advanced solid tumors.
Authors: Gordon MS, Sweeney CS, Mendelson DS
Clin. Cancer Res., 2010;16(2):699-710.
Species: Human
Sample Type: Plasma
Application: Electrochemiluminescent Assay
Soluble c-Met receptors inhibit phosphorylation of c-Met and growth of hepatocyte growth factor: c-Met-dependent tumors in animal models.
Authors: Coxon A, Rex K, Meyer S, Sun J, Sun J, Chen Q, Radinsky R, Kendall R, Burgess TL
Mol. Cancer Ther., 2009;0(0):.
Species: Human
Sample Type: Cell Lysates
Application: Electrochemiluminescence

HGF R, also known as Met (from N-methyl-N’-nitro-N-nitrosoguanidine induced), is a glycosylated receptor tyrosine kinase that plays a central role in epithelial morphogenesis and cancer development. HGF R is synthesized as a single chain precursor which undergoes cotranslational proteolytic cleavage. This generates a mature HGF R that is a disulfide-linked dimer composed of a 50 kDa extracellular alpha chain and a 145 kDa transmembrane beta chain (1, 2). The extracellular domain (ECD) contains a seven bladed beta -propeller sema domain, a cysteine-rich PSI/MRS, and four Ig-like E-set domains, while the cytoplasmic region includes the tyrosine kinase domain (3, 4). Proteolysis and alternate splicing generate additional forms of human HGF R which either lack the kinase domain, consist of secreted extracellular domains, or are deficient in proteolytic separation of the alpha and beta chains (5-7). The sema domain, which is formed by both the alpha and beta chains of HGF R, mediates both ligand binding and receptor dimerization (3, 8). Ligand-induced tyrosine phosphorylation in the cytoplasmic region activates the kinase domain and provides docking sites for multiple SH2-containing molecules (9, 10). HGF stimulation induces HGF R downregulation via internalization and proteasome-dependent degradation (11). In the absence of ligand, HGF R forms noncovalent complexes with a variety of membrane proteins including CD44v6, CD151, EGF R, Fas, Integrin alpha 6/ beta 4, Plexins B1, 2, 3, and MSP R/Ron (12-19). Ligation of one complex component triggers activation of the other, followed by cooperative signaling effects (12-19). Formation of some of these heteromeric complexes is a requirement for epithelial cell morphogenesis and tumor cell invasion (12, 16, 17). Paracrine induction of epithelial cell scattering and branching tubulogenesis results from the stimulation of HGF R on undifferentiated epithelium by HGF released from neighboring mesenchymal cells (20). Genetic polymorphisms, chromosomal translocation, overexpression, and additional splicing and proteolytic cleavage of HGF R have been described in a wide range of cancers (1). Within the ECD, human HGF R shares 86-88% aa sequence identity with canine, mouse, and rat HGF R.

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