Agonist Met antibodies define the signalling threshold required for a full mitogenic and invasive program of Kaposi's Sarcoma cells.
We previously showed that the Kaposi Sarcoma line KS-IMM express a functional Met tyrosine kinase receptor, which, upon HGF stimulation, activates motogenic, proliferative, and invasive responses. In this study, we investigated the signalling pathways activated by HGF, as well as by Met monoclonal antibodies (Mabs), acting as full or partial agonists. The full agonist Mab mimics HGF in all biological and biochemical aspects. It elicits the whole spectrum of responses, while the partial agonist Mab induces only wound healing. These differences correlated with a more prolonged and sustained tyrosine phosphorylation of the receptor and MAPK evoked by HGF and by the full agonist Mab, relative to the partial agonist Mab. Since Gab1, JNK and PI 3-kinase are activated with same intensity and kinetics by HGF and by the two agonist antibodies, it is concluded that level and duration of MAPK activation by Met receptor are crucial for the induction of a full HGF-dependent mitogenic and invasive program in KS cells.
Bardelli
Claudio
C
Dipt. Scienze Mediche, Università del Piemonte Orientale A. Avogadro Via Solaroli 17, 28100 Novara, Italy.
Sala
Marilena
M
Cavallazzi
Umberto
U
Prat
Maria
M
D000906:Antibodies / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D004056:Differential Threshold; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008934:Mitogens / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor / Q000276:immunology / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
D000906:Antibodies; C066855:HGF protein, human; D008934:Mitogens; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D020928:Mitogen-Activated Protein Kinases