Inhibition of matrix metalloproteinase 9 expression by a ribozyme blocks metastasis in a rat sarcoma model system.
Inhibition of matrix metalloproteinase 9 expression by a ribozyme blocks metastasis in a rat sarcoma model system.
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发表时间：
1996-11
期刊：
影响因子：
11.2
通讯作者：
Jin Hua;R. Muschel
中科院分区：
文献类型：
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作者：
Jin Hua;R. Muschel
基质金属蛋白酶(MMPs)已被认为与肿瘤的进展有关，但该家族的每个成员在恶性肿瘤行为中可能扮演的确切角色才刚刚开始被了解。明胶酶B或92-kDa明胶酶/IV型胶原酶)的表达与多种模型系统的转移有关，其中包括用RASH和MyC转化大鼠胚胎细胞所产生的大鼠肉瘤。为了确定基质金属蛋白酶-9的表达在这个系统中的作用，我们用锤头状核酶抑制了基质金属蛋白酶-9的表达。将针对大鼠基质金属蛋白酶-9基因序列的核酶表达载体导入rash和myc(2.10.10)诱导性分泌基质金属蛋白酶-9的转移大鼠胚胎细胞系，可导致可检测到的基质金属蛋白酶-9基因的缺失和释放的92 kDa明胶酶活性丧失。这些细胞在肺定植试验中不再转移，但仍具有致瘤性。为对照锤头状核酶引入表达载体没有效果。这些数据证明了在该系统中转移过程中对基质金属蛋白酶-9表达的要求。
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.