title: The Dual Inhibition of Met and EGFR by ME22S, a Novel Met/EGFR Bispecific Monoclonal Antibody, Suppresses the Proliferation and Invasion of Laryngeal Cancer.
abstract: It has been reported that the abnormal activation of receptor tyrosine kinases is associated with the development of many human carcinomas and the high activation of EGFR and Met mediates the tumorigenicity of laryngeal carcinoma. In this study, we have done the therapeutic efficacy of ME22S (a novel EGFR/Met bispecific antibody) in laryngeal carcinoma in vitro and in vivo was thoroughly evaluated.
  
  
  
  The effects of ME22S on cell viability was assessed through MTT assays, and then Western blotting and immunocytochemistry were used to determine the expression of EGFR and Met. Also, wound healing and invasion assays were performed to observe the inhibitory effects of ME22S.
  
  
  
  We found the ability of ME22S reducing the expression of both EGFR and Met and significantly inhibiting the cell migration, invasion, and proliferation of SNU899 and HN3 in vitro. Also, the notably reduced levels of p-Met, p-ERK, and p-AKT were found when the cells were treated with only ME22S alone or with HGF together. Meanwhile, ME22S, interestingly enough, caused caspase-3-dependent apoptotic cell death when HN3 cells were treated with ME22S for 72 h, decreased the HGF-induced Slug expression, and also inhibited the tumor growth of HN3 cells in a xenograft model in vivo.
  
  
  
  Taken together, our findings suggest that the dual inhibition of EGFR and Met through ME22S largely suppresses the invasion and growth of laryngeal carcinoma both in vitro and in vivo, hence, can be a practical approach as a novel therapeutic strategy for the treatment of laryngeal carcinoma.
authors.affiliation: Department of Otolaryngology, School of Medicine, Suwon, Republic of Korea.
authors.forename: Bok-Soon
authors.initials: BS
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, School of Medicine, Suwon, Republic of Korea.|Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Haeng-Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Suwon, Republic of Korea.
authors.forename: Jae-Woong
authors.initials: JW
authors.lastname: Hwang
authors.affiliation: Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Suwon, Republic of Korea.
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Cheong
authors.affiliation: Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Suwon, Republic of Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, School of Medicine, Suwon, Republic of Korea.
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Cha
authors.affiliation: Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology (SAIT), Suwon, Republic of Korea.
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, School of Medicine, Suwon, Republic of Korea. ostium@ajou.ac.kr.|Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea. ostium@ajou.ac.kr.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D018033:Antibodies, Bispecific; D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met