Hua J, Muschel R J
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Cancer Res. 1996 Nov 15;56(22):5279-84.
Matrix metalloproteinases (MMPs) have been implicated in tumor progression, but the exact roles that each member of this family may play in contributing to the behavior of malignant tumors are only beginning to be understood. MMP-9 (gelatinase B or the 92-kDa gelatinase/type IV collagenase) expression has been associated with metastasis in a variety of model systems including that of rat sarcomas generated by transformation of rat embryo cells with rasH and myc. To determine the effect that expression of MMP-9 has in this system, we inhibited the expression of MMP-9 using a hammerhead ribozyme. Introduction of an expression vector for a ribozyme directed against the rat MMP-9 mRNA sequence into a metastatic rat embryo cell line transformed by rasH and myc (2.10.10) that constitutively secretes MMP-9 resulted in the absence of detectable MMP-9 mRNA and loss of released 92-kDa gelatinase activity. These cells were no longer metastatic in a lung colonization assay but retained tumorigenicity. Introduction of an expression vector for a control hammerhead ribozyme had no effect. These data document the requirement for MMP-9 expression in metastasis in this system.
基质金属蛋白酶（MMPs）与肿瘤进展有关，但该家族每个成员在恶性肿瘤行为中的确切作用才刚刚开始被了解。MMP-9（明胶酶B或92 kDa明胶酶/IV型胶原酶）的表达已在多种模型系统中与转移相关，包括用rasH和myc转化大鼠胚胎细胞产生的大鼠肉瘤模型。为了确定MMP-9表达在该系统中的作用，我们使用锤头状核酶抑制MMP-9的表达。将针对大鼠MMP-9 mRNA序列的核酶表达载体导入由rasH和myc转化的转移性大鼠胚胎细胞系（2.10.10）中，该细胞系组成性分泌MMP-9，结果导致无法检测到MMP-9 mRNA，并丧失了释放的92 kDa明胶酶活性。这些细胞在肺定植试验中不再具有转移性，但保留了致瘤性。导入对照锤头状核酶的表达载体没有效果。这些数据证明了该系统中转移需要MMP-9的表达。
