INCREASED EXPRESSION OF MEMBRANE TYPE 1-MATRIX METALLOPROTEINASE IN HEAD AND NECK-CARCINOMA

BACKGROUND. Three types of membrane type-matrix metalloproteinases (MT -MMPs) have been identified as activators of pro-MMP2 (gelatinase A/72 -kilodalton Type nr collagenase), which is believed to be crucial for tumor invasion and metastasis. MT1-MMP has been shown to be widely exp ressed in various tissues and to be overexpressed in lung and gastric carcinomas. METHODS. Activation of pro-MMP2 was examined in head and n eck squamous cell carcinoma (HNSCC) by gelatin zymography. The express ion of the MT1-MMP mRNA transcript was studied by Northern hybridizati on and that of MT1-MMP protein by immunohistochemical staining with a monoclonal antibody against MT1-MMP. RESULTS, Activation of pro-MMP2 w as observed in ten of ten HNSCC tissues. Increased expression of the M T1-MMP mRNA transcript was also detected in eight of eight of these ti ssues. MT1-MMP positive cells were detected at the tumor cell lesions in the majority of these carcinoma tissues by immunohistochemical stai ning (24 of 27). MT1-MMP expression was more intense in moderately and well differentiated tumors than in poorly differentiated ones (P < 0. 05). CONCLUSIONS. These results suggest that MT1-MMP is involved in th e activation of pro-MMP2 in HNSCC. These findings suggest that MT1-MMP is significant not only as a tumor marker but as a new target for che motherapy against HNSCC. (C) 1997 American Cancer Society.