Matrix metalloproteinase-8 functions as a metastasis suppressor through modulation of tumor cell adhesion and invasion
Matrix metalloproteinase-8 functions as a metastasis suppressor through modulation of tumor cell adhesion and invasion
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DOI：
10.1158/0008-5472.can-07-5154
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发表时间：
2008-04-15
期刊：
影响因子：
11.2
通讯作者：
Lopez-Otin, Carlos
中科院分区：
文献类型：
--
作者：
Gutierrez-Fernandez, Ana;Fueyo, Antonio;Lopez-Otin, Carlos
胶原酶-2 （matrix metalloproteinase-8, MMP-8）是一种主要由中性粒细胞产生的MMP，与多种炎症有关。我们之前已经描述过MMP-8通过其调节致癌物诱导的炎症反应的能力在癌症中发挥保护作用。此外，据报道，实验操作这种酶的表达水平改变了人类乳腺癌细胞的转移行为。在这项工作中，我们使用MMP-8缺失的突变小鼠和过表达该酶的同基因黑色素瘤和肺癌肿瘤细胞系来进一步探索MMP-8的抗转移潜力。我们在此报道MMP-8通过调节肿瘤细胞的粘附和侵袭来阻止转移的形成。因此，过表达MMP-8的肿瘤细胞与细胞外基质蛋白的粘附性增加，而与对照细胞相比，其通过Matrigel的侵袭能力大大降低。对乳腺癌患者的MMP-8的分析表明，乳腺癌肿瘤中MMP-8金属蛋白酶的表达与淋巴结转移发生率较低相关，并能给这些患者带来良好的预后。在此基础上，我们提出MMP-8是一种肿瘤保护因子，在小鼠和人体内都具有降低恶性细胞转移潜能的能力。
Collagenase-2 (matrix metalloproteinase-8, MMP-8) is an MMP mainly produced by neutrophils and associated with many inflammatory conditions. We have previously described that MMP-8 plays a protective role in cancer through its ability to regulate the inflammatory response induced by carcinogens. Moreover, it has been reported that experimental manipulation of the expression levels of this enzyme alters the metastatic behavior of human breast cancer cells. In this work, we have used mutant mice deficient in MMP-8 and syngenic melanoma and lung carcinoma tumor cells lines overexpressing this enzyme to further explore the putative antimetastatic potential of MMP-8. We report herein that MMP-8 prevents metastasis formation through the modulation of tumor cell adhesion and invasion. Thus, tumor cells overexpressing MMP-8 have an increased adhesion to extracellular matrix proteins, whereas their invasive ability through Matrigel is substantially reduced when compared with control cells. Analysis of MMP-8 in breast cancer patients revealed that the expression of this metalloproteinase by breast tumors correlates with a lower incidence of lymph node metastasis and confers good prognosis to these patients. On this basis, we propose that MMP-8 is a tumor protective factor, which also has the ability to reduce the metastatic potential of malignant cells in both mice and human.