Suzuki Tomotaka, Kuwabara Yoshiyuki, Iwata Hiroji, Mitani Masami, Shinoda Noriyuki, Sato Atsushi, Mitsui Akira, Sugiura Masahiko, Kato Joji, Fujii Yoshitaka
Department of Surgery II, Nagoya City University Medical School, Mizuho-Cho, Mizuho-Ku, Nagoya, Aichi, Japan.
J Surg Oncol. 2002 Oct;81(2):80-6. doi: 10.1002/jso.10134.
Although some investigators recently suggested that MMP-9 may play a critical role in invasion and metastasis, along with MMP-2, in esophageal carcinoma, there has been no direct evidence that MMPs play a critical role in the actual invasion of esophageal carcinoma cells. Here, we investigated the role of MMPs in the in vitro invasion of esophageal carcinoma cell lines (TE-series).
Our methods included in vitro invasion assay, gelatin zymography, and enzyme-linked immunosorbent assay (ELISA).
Four cell lines (but not TE-5) secreted MMP-2 and MMP-9 in the culture medium. Using a quantitative in vitro invasion assay, we found a significant (P = 0.002) correlation between the extent of in vitro invasion and the amount of MMP-9, but not of MMP-2, secreted into the conditioned medium in the four cell lines. In these cell lines, R-94138, a specific MMP-9 inhibitor, inhibited in vitro invasion in a dose-dependent manner. Although TE-5 did not secrete MMP-2 or MMP-9, the cells showed a strong in vitro invasion.
Our data suggest that most of the esophageal carcinoma cell lines use MMP-9 for in vitro invasion, but others may use proteinase(s) other than MMP-9.
尽管近期一些研究人员提出，基质金属蛋白酶-9（MMP-9）可能与基质金属蛋白酶-2（MMP-2）一起在食管癌的侵袭和转移过程中发挥关键作用，但尚无直接证据表明基质金属蛋白酶在食管癌细胞的实际侵袭过程中起关键作用。在此，我们研究了基质金属蛋白酶在食管癌细胞系（TE系列）体外侵袭中的作用。
我们的方法包括体外侵袭试验、明胶酶谱法和酶联免疫吸附测定（ELISA）。
四种细胞系（但不包括TE-5）在培养基中分泌MMP-2和MMP-9。通过定量体外侵袭试验，我们发现四种细胞系中，体外侵袭程度与条件培养基中分泌的MMP-9量之间存在显著相关性（P = 0.002），而与MMP-2量无关。在这些细胞系中，特异性MMP-9抑制剂R-94138以剂量依赖方式抑制体外侵袭。尽管TE-5不分泌MMP-2或MMP-9，但该细胞系表现出较强的体外侵袭能力。
我们的数据表明，大多数食管癌细胞系在体外侵袭中利用MMP-9，但其他细胞系可能利用MMP-9以外的蛋白酶。
