Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor
Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor
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DOI：
10.1038/sj.cr.7310089
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发表时间：
2006-09-01
期刊：
影响因子：
44.1
通讯作者：
Sang, Qing-Xiang Amy
中科院分区：
文献类型：
--
作者：
Lee, Seakwoo;Desai, Kevin K.;Sang, Qing-Xiang Amy
识别用于早期前列腺癌诊断的新型生物标志物是非常重要的，因为早期检测和治疗对于患者的医疗管理至关重要。基底细胞层和基底膜的连续性的破坏对于人类前列腺中高级别前列腺上皮内瘤变（HGPIN）向浸润性腺癌的进展是必不可少的。参与转化为侵袭性表型的分子是严格审查的主题。我们以前曾报道，基质金属蛋白酶-26（MMP-26）通过切割基底膜蛋白和激活MMP-9的酶原形式促进人前列腺癌细胞的侵袭。此外，我们发现金属蛋白酶组织抑制剂-4（TIMP-4）是MMP-26最有效的内源性抑制剂。在此，我们证实了MMP-26和TIMP-4在HGPIN和肿瘤中的表达高于非肿瘤性腺泡（p < 0.0001）。它们的表达水平在HGPIN中最高，但在相同组织中的浸润性癌中下降（每种p < 0.001）。连续前列腺癌组织切片的免疫组织化学染色表明MMP-26和TIMP-4共定位。本研究提示MMP-26和TIMP-4在HGPIN向浸润性前列腺癌的转化过程中起重要作用，并可作为前列腺癌早期诊断的标志物。
The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia (HGPIN) to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 (MMP-26) promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 (TIMP-4) is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher (p < 0.0001) MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer (p < 0.001 for each) in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.