Yoshizaki T, Sato H, Maruyama Y, Murono S, Furukawa M, Park C S, Seiki M
Department of Otolaryngology, School of Medicine, Kanazawa University, Japan.
Cancer. 1997 Jan 1;79(1):139-44. doi: 10.1002/(sici)1097-0142(19970101)79:1<139::aid-cncr20>3.0.co;2-4.
Three types of membrane type-matrix metalloproteinases (MT-MMPs) have been identified as activators of pro-MMP2 (gelatinase A/72-kilodalton Type IV collagenase), which is believed to be crucial for tumor invasion and metastasis. MT1-MMP has been shown to be widely expressed in various tissues and to be overexpressed in lung and gastric carcinomas.
Activation of pro-MMP2 was examined in head and neck squamous cell carcinoma (HNSCC) by gelatin zymography. The expression of the MT1-MMP mRNA transcript was studied by Northern hybridization and that of MT1-MMP protein by immunohistochemical staining with a monoclonal antibody against MT1-MMP.
Activation of pro-MMP2 was observed in ten of ten HNSCC tissues. Increased expression of the MT1-MMP mRNA transcript was also detected in eight of eight of these tissues. MT1-MMP positive cells were detected at the tumor cell lesions in the majority of these carcinoma tissues by immunohistochemical staining (24 of 27). MT1-MMP expression was more intense in moderately and well differentiated tumors than in poorly differentiated ones (P < 0.05).
These results suggest that MT1-MMP is involved in the 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 chemotherapy against HNSCC.
三种膜型基质金属蛋白酶（MT-MMPs）已被确定为前MMP2（明胶酶A/72千道尔顿IV型胶原酶）的激活剂，前MMP2被认为对肿瘤侵袭和转移至关重要。MT1-MMP已被证明在各种组织中广泛表达，并在肺癌和胃癌中过表达。
通过明胶酶谱法检测头颈部鳞状细胞癌（HNSCC）中前MMP2的激活情况。通过Northern杂交研究MT1-MMP mRNA转录本的表达，并用抗MT1-MMP单克隆抗体通过免疫组织化学染色研究MT1-MMP蛋白的表达。
在所有10例HNSCC组织中均观察到前MMP2的激活。在其中8例组织中也检测到MT1-MMP mRNA转录本表达增加。通过免疫组织化学染色在大多数这些癌组织的肿瘤细胞病变处检测到MT1-MMP阳性细胞（27例中的24例）。MT1-MMP在中分化和高分化肿瘤中的表达比低分化肿瘤更强烈（P<0.05）。
这些结果表明MT1-MMP参与了HNSCC中前MMP2的激活。这些发现表明MT1-MMP不仅作为一种肿瘤标志物具有重要意义，而且作为针对HNSCC的化疗新靶点也具有重要意义。
