Evidence for increased activated metalloproteinase 2 (MMP-2a) expression associated with human prostate cancer progression.
Evidence for increased activated metalloproteinase 2 (MMP-2a) expression associated with human prostate cancer progression.
复制标题
DOI：
--
复制
发表时间：
1996
影响因子：
3.1
通讯作者：
M. Stearns;Stearns Me
中科院分区：
文献类型：
--
作者：
M. Stearns;Stearns Me
免疫标记研究此前表明，72 kDa 基质金属蛋白酶 2 (MMP-2) 表达增加与人类前列腺癌进展相关。目前尚不清楚具有酶活性的 MMP-2 是否在前列腺癌中表达，以及表达增加是否与进展相关。使用对活化的 MMP-2 分子（MMP-2a，66 kDa）具有特异性的单克隆抗体（以及之前开发的 MMP-2 抗体）来研究人前列腺组织提取物中 MMP-2a 和 MMP-2 的表达。 SDS-PAGE、蛋白质印迹和酶谱表明，在正常前列腺 (n = 6)、良性前列腺增生 (n = 9) 和低格里森评分 (GS) 4 的前列腺癌 (n = 11) 中检测不到 MMP-2a 表达。 MMP-2a 在 GS 增加的前列腺癌 (n = 37) 和淋巴结转移 (n = 7) 中表达。人类前列腺癌组织提取物的定量 ELISA 显示，在 GS 增加的前列腺癌组织中，每微克蛋白质的 MMP-2 和 MMP-2a 水平增加 (n = 48)。 MMP-2a 水平在前列腺淋巴结转移中也很高，但 MMP-2 在这些组织中不表达或几乎检测不到。在GS 4至10的组织中，MMP-2a与MMP-2的摩尔比分别从0增加至6.23。我们得出的结论是，MMP-2a 的显着增加与前列腺癌的恶性进展以及肿瘤细胞转移至淋巴结有关。
Immunolabeling studies have previously indicated that increased expression of the 72-kDa matrix metalloproteinase 2 (MMP-2) is associated with human prostate cancer progression. It is not known if the enzymatically active MMP-2 is expressed in prostate cancer and if increased expression is associated with progression. Monoclonal antibodies specific for the activated MMP-2 molecule (MMP-2a, 66 kDa) were used (along with previously developed MMP-2 antibodies) to investigate the expression of MMP-2a and MMP-2 in human prostate tissue extracts. SDS-PAGE, Western blots, and zymography indicated that MMP-2a expression was undetectable in normal prostate (n = 6), benign prostatic hyperplasia (n = 9), and in prostate cancer of low Gleason score (GS) 4 (n = 11). MMP-2a was expressed in prostate cancer of increased GS (n = 37) and in lymph node metastases (n = 7). Quantitative ELISAs of human prostate cancer tissue extracts revealed that the levels of MMP-2 and MMP-2a per microgram of protein increased in prostate cancer tissues of increased GS (n = 48). MMP-2a levels were also high in prostatic lymph node metastases, but MMP-2 was not expressed or was barely detectable in these tissues. The molar ratios of MMP-2a to MMP-2 increased from 0 to 6.23 in tissues of GS 4 to 10, respectively. We conclude that significant increases in MMP-2a are associated with the malignant progression of prostate cancer and with tumor cell metastases to lymph nodes.