Met degradation by SAIT301, a Met monoclonal antibody, reduces the invasion and migration of nasopharyngeal cancer cells via inhibition of EGR-1 expression.
Nasopharyngeal carcinoma (NPC) is a common malignant tumor with high invasive and metastatic potential. The hepatocyte growth factor (HGF)-Met signaling pathway has a critical role in mediating the invasive growth of many different types of cancer, including head and neck squamous cell carcinoma. HGF also stimulates NPC cell growth and invasion in the cell line model. In this study, we determined the inhibitory effect of Met, using a Met-targeting monoclonal antibody (SAIT301), on the invasive and growth potential of NPC cell lines. Met inhibition by SAIT301 resulted in highly significant inhibition of cell migration and invasion in both the HONE1 and HNE1 cell lines. In addition, we also found that co-treatment of SAIT301 and HGF decreased the anchorage-independent growth induced by HGF in HNE1 cell lines. After SAIT301 treatment, Met, together with its downstream signaling proteins, showed downregulation of p-Met and p-ERK, but not p-AKT, in both HONE1 and HNE1 cell lines. Interestingly, we found that HGF treatment of NPC cell lines induced early growth response protein (EGR-1) expression, which is involved in cell migration and invasion. In addition, co-treatment with SAIT301 and HGF inhibited the HGF-induced expression of EGR-1. Next, knockdown of EGR-1 using small-interfering RNA inhibited HGF-induced cell invasion in NPC cell lines, suggesting that the expression level of EGR-1 is important in HGF-induced cell invasion of NPC cells. Therefore, the results support that SAIT301 inhibited Met activation as well as the downstream EGR-1 expression and could have therapeutic potential in NPC. Taken together, we suggest that Met is an anticancer therapeutic target for NPC that warrants further investigation and clinical trials and SAIT301 may be a promising tool for NPC therapy.
1] Department of Otolaryngology, Ajou University, Suwon, Republic of Korea [2] Center for Cell Death Regulating Biodrug, School of Medicine, Ajou University, Suwon, Republic of Korea.
B-S
BS
Lee
1] Department of Otolaryngology, Ajou University, Suwon, Republic of Korea [2] Center for Cell Death Regulating Biodrug, School of Medicine, Ajou University, Suwon, Republic of Korea [3] Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
S
S
Kang
Bio Therapeutics Lab, Samsung Advanced Institute of Technology (SAIT)/Samsung Electronics Co. Ltd, Yongin, Republic of Korea.
K-A
KA
Kim
Bio Therapeutics Lab, Samsung Advanced Institute of Technology (SAIT)/Samsung Electronics Co. Ltd, Yongin, Republic of Korea.
Y-J
YJ
Song
Bio Therapeutics Lab, Samsung Advanced Institute of Technology (SAIT)/Samsung Electronics Co. Ltd, Yongin, Republic of Korea.
K H
KH
Cheong
1] Department of Otolaryngology, Ajou University, Suwon, Republic of Korea [2] Center for Cell Death Regulating Biodrug, School of Medicine, Ajou University, Suwon, Republic of Korea.
H-Y
HY
Cha
1] Department of Otolaryngology, Ajou University, Suwon, Republic of Korea [2] Center for Cell Death Regulating Biodrug, School of Medicine, Ajou University, Suwon, Republic of Korea [3] Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
C-H
CH
Kim
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D002277:Carcinoma; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D059748:Proteolysis / Q000187:drug effects*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D051766:Early Growth Response Protein 1; D034741:RNA, Small Interfering; C000597195:SAIT301; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met