Shima I, Sasaguri Y, Kusukawa J, Nakano R, Yamana H, Fujita H, Kakegawa T, Morimatsu M
Department of Pathology, Kurume University School of Medicine, Japan.
Br J Cancer. 1993 Apr;67(4):721-7. doi: 10.1038/bjc.1993.132.
We demonstrated that four human oesophageal squamous cell carcinoma cell lines (TE8, TE9, TE10 and TE11) produced matrix metalloproteinase-1 (proMMP-1/tissue collagenase), 2 (ProMMP-2/'type IV collagenase'), 3 (proMMP-3/stromelysin), and 9 (proMMP-9/92-kDa gelatinase) as members of a matrix metalloproteinase (MMP) family, which degrades extracellular matrix macromolecules. Under normal culture conditions, in immunoblot analysis, proMMP-1 of M(r) = 53,00 was detected in one cell line (TE8), proMMP-2 of M(r) = 72,000 in three cell lines (TE9, TE10, and TE11), and proMMP-3 of M(r) = 57,000 in all four cell lines. In addition to these enzymes, in enzymography, a gelatinolytic activity around M(r) = 92-kDa, likely to be proMMP-9, was detected in only one cell line (TE10) under normal culture conditions. When these cell lines were treated with epidermal growth factor (EGF), however, the agent stimulated three cell lines (TE8, TE10 and TE11) to produce proMMP-9 in a dose-dose dependent manner. Oesophageal carcinoma-conditioned medium stimulated oesophageal fibroblasts to produce proMMP-1, -2, and -3, suggesting that the interaction between oesophageal carcinoma and stromal fibroblasts also plays a role in the production of MMPs by the latter. Our present study illustrates that oesophageal squamous cell carcinoma produces a variety of MMPs including proMMP-1, -2, -3, and -9 in vitro, suggesting that the ability of MMP production of the tumour may play an important role in its malignant behaviour and that the production of proMMP-9 may be regulated by EGF via overexpression of EGF receptors.
我们证明，四种人食管鳞状细胞癌细胞系（TE8、TE9、TE10和TE11）可产生基质金属蛋白酶-1（前MMP-1/组织胶原酶）、2（前MMP-2/IV型胶原酶）、3（前MMP-3/基质溶解素）和9（前MMP-9/92 kDa明胶酶），它们均为基质金属蛋白酶（MMP）家族成员，可降解细胞外基质大分子。在正常培养条件下，免疫印迹分析显示，在一个细胞系（TE8）中检测到相对分子质量（M(r)）为53,000的前MMP-1，在三个细胞系（TE9、TE10和TE11）中检测到M(r)为72,000的前MMP-2，在所有四个细胞系中均检测到M(r)为57,000的前MMP-3。除了这些酶，在酶谱分析中，正常培养条件下仅在一个细胞系（TE10）中检测到一种M(r)约为92 kDa的明胶酶解活性，可能是前MMP-9。然而，当用表皮生长因子（EGF）处理这些细胞系时，该因子以剂量依赖方式刺激三个细胞系（TE8、TE10和TE11）产生前MMP-9。食管癌条件培养基刺激食管成纤维细胞产生前MMP-1、-2和-3，这表明食管癌与基质成纤维细胞之间的相互作用在后者产生MMP的过程中也发挥作用。我们目前的研究表明，食管鳞状细胞癌在体外可产生多种MMP，包括前MMP-1、-2、-3和-9，这表明肿瘤产生MMP的能力可能在其恶性行为中起重要作用，并且前MMP-9的产生可能受EGF通过EGF受体的过表达调控。
