Activation of matrix metalloproteinase-2 in head and neck squamous cell carcinoma: studies of clinical samples and in vitro cell lines co-cultured with fibroblasts.
We undertook this present study to investigate the activation of matrix metalloproteinase-2 (MMP-2) in human head and neck squamous cell carcinomas (HNSCC) tissues and cell lines. Gelatinolytic activities of active MMP-2 were significantly higher in carcinoma samples than in normal portions. Furthermore, the activation ratio of proMMP-2 significantly correlated with cervical lymph node metastasis. In vitro studies revealed an HNSCC cell line, HEp-2, to produce neither the pro form nor the active form of MMP-2, but human fibroblasts were found to produce proMMP-2. However, coculture of HEp-2 cells with fibroblasts resulted in the production of not only proMMP-2 but also activeMMP-2 in the culture medium. Northern blot analysis revealed a stronger expression of membrane-type 1 matrix metalloproteinase (MT1-MMP),which is a specific activator of MMP-2, mRNA in HEp-2 cells than in fibroblasts. These results suggest the activation of proMMP-2 as an important event in the process of HNSCC metastasis. They also suggest MMP-2 is secreted in its pro form by stromal fibroblasts surrounding the cancer cells and activated by MT1-MMP localized on the cancer cells.
Tokumaru
Y
Y
Department of Otolaryngology, School of Medicine, Keio University, Tokyo, Japan.
Fujii
M
M
Otani
Y
Y
Kameyama
K
K
Imanishi
Y
Y
Igarashi
N
N
Kanzaki
J
J
D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005347:Fibroblasts; D005780:Gelatin / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D005780:Gelatin; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2