Overexpression of c-Met promotes invasion and metastasis of small oral tongue carcinoma.
c-Met proto-oncogene, which is a receptor of ligand hepatocyte growth factor (HGF), has been associated with cancer cell invasion. There have been no reports on the relationship between the expression of c-Met and tumor invasion and metastasis in small (T(1-2)) squamous cell carcinoma of the oral tongue (SCCOT). We analyzed the relationship between c-Met expression and tumor invasion depth and lymph node metastasis in 71 surgically treated patients with small SCCOT using immunohistochemistry. Furthermore, we investigated the associations between the c-Met expression status and patient survival. In addition, we explored whether overexpression of c-Met enhances tumor growth and invasion of tongue cancer cells in vitro and in vivo. Positive immunohistochemical staining of c-Met was observed in 39 (55%) samples. Presence of neck metastasis, and >4mm depth of tumor invasion, strongly correlated with c-Met expression in small SCCOT both by the univariate and multivariate analysis (p<.05). The survival rates with c-Met expression were significantly shorter than for patients without c-Met expression (p<.05). Constitutive activation of c-Met enhanced migration and invasion of tongue cancer cells in vitro through the expressions of matrix metalloproteinase-1, -2, and -9, and promoted tongue cancer cell growth in vitro and in vivo. The results support the association of c-Met with the invasiveness and metastasis of small SCCOT.
Department of Otorhinolaryngology - Head and Neck Surgery, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
Young Chang
YC
Lim
Jae Ho
JH
Han
Hyun Jung
HJ
Kang
Young Sook
YS
Kim
Bum Hei
BH
Lee
Eun Chang
EC
Choi
Chul-Ho
CH
Kim
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009333:Neck; D009361:Neoplasm Invasiveness; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1