Requirement for matrix metalloproteinase-9 (gelatinase B) expression in metastasis by murine prostate carcinoma.
Requirement for matrix metalloproteinase-9 (gelatinase B) expression in metastasis by murine prostate carcinoma.
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发表时间：
1998-02
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通讯作者：
Geeta Sehgal;Jin Hua;E. Bernhard;I. Sehgal;Timothy C. Thompson;R. Muschel
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作者：
Geeta Sehgal;Jin Hua;E. Bernhard;I. Sehgal;Timothy C. Thompson;R. Muschel
虽然一些有效的治疗方法可用于局限性前列腺癌，但转移性前列腺癌难以治疗且不可能治愈。识别使前列腺癌细胞转移的基因产物有助于理解导致转移的过程。为了表征基质金属蛋白酶-9（MMP-9、明胶酶B或92 kd IV型明胶酶/胶原酶）对前列腺癌转移发展的贡献，我们使用核酶降低转移性小鼠前列腺癌细胞中MMP-9的表达。与亲本细胞或对照转染子相比，核酶转染的细胞具有较低的MMP-9基础水平以及在转化生长因子-β或佛波醇12-肉豆蔻酸酯13-乙酸酯刺激后降低的水平。MMP-9下调的细胞在实验转移测定中不能形成肺集落，而对照和亲本细胞容易形成转移。所有细胞类型在注射后都容易形成肿瘤，MMP-9的下调对肿瘤生长速率没有不利影响。因此，MMP-9的表达需要在小鼠前列腺模型系统的血行转移，提高了它可能在人类前列腺癌中发挥同等作用的可能性。
Although a number of effective therapies are available for localized prostate cancer, metastatic prostate cancer is difficult to treat and impossible to cure. Identification of the gene products that enable a prostatic carcinoma cell to metastasize should facilitate an understanding of the processes leading to metastasis. To characterize the contribution of matrix metalloproteinase-9 (MMP-9, gelatinase B or the 92-kd type IV gelatinase/collagenase) to the development of metastasis in prostate cancer, we reduced MMP-9 expression in metastatic murine prostatic carcinoma cells using a ribozyme. The ribozyme transfected cells had lower basal levels of MMP-9 as well as decreased levels after stimulation by transforming growth factor-beta or phorbol 12-myristate 13-acetate when compared with the parental cells or with control transfectants. The cells with down-regulated MMP-9 were unable to form lung colonies in the experimental metastasis assay, whereas the controls and parental cells readily formed metastases. All cell types readily formed tumors after injection and down-regulation of MMP-9 did not adversely affect the rate of tumor growth. Thus, MMP-9 expression is required for hematogenous metastasis in a murine prostate model system raising the possibility that it may play an equivalent role in human prostate cancer.