Earlier onset of tumoral anglogenesis in matrix metalloproteinase-19-deficient mice
Earlier onset of tumoral anglogenesis in matrix metalloproteinase-19-deficient mice
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DOI：
10.1158/0008-5472.can-05-4315
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发表时间：
2006-05-15
期刊：
影响因子：
11.2
通讯作者：
Noel, Agnes
中科院分区：
文献类型：
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作者：
Jost, Maud;Folgueras, Alicia R.;Noel, Agnes
在基质金属蛋白酶中，基质金属蛋白酶-19具有独特的结构特征和组织分布。与大多数基质金属蛋白酶不同，基质金属蛋白酶-19在正常人表皮中表达，在恶变和去分化过程中表达下调。基质金属蛋白酶-19在肿瘤血管生成中的作用目前尚不清楚。为了对基质金属蛋白酶-19在体内的功能有新的认识，分析了小鼠恶性PDVA角质形成细胞移植和注射Matrigel加碱性成纤维细胞生长因子后，缺失基质金属蛋白酶-19突变小鼠的血管生成反应。原位杂交和免疫组织化学分析显示，基质金属蛋白酶-19由宿主间充质细胞产生，而不是由内皮毛细血管细胞或CD11b阳性的炎症细胞产生。基于一种新的计算机辅助定量方法，我们提供了宿主基质金属蛋白酶-19缺乏与早期血管生成反应增加相关的证据。此外，在MMP-19-/-小鼠中观察到肿瘤侵袭力的增加。我们的结论是，与大多数促进肿瘤进展的MMPs不同，MMP19是肿瘤血管生成和侵袭的早期负调控因子。这些数据强调了了解每个NIMP的单独功能以改进抗癌策略的必要性。
Among matrix metalloproteinases (MAIP), MMP-19 displays unique structural features and tissue distribution. In contrast to most MMPs, MMP-19 is expressed in normal human epidermis and down-regulated during malignant transformation and dedifferentiation. The contribution of MMP-19 during tumor angiogenesis is presently unknown. In an attempt to give new insights into MMP-19 in vivo functions, angiogenic response of mutant mice lacking MMP-19 was analyzed after transplantation of murine malignant PDVA keratinocytes and after injection of Matrigel supplemented with basic fibroblast growth factor. In situ hybridization and immunohistochemical analysis revealed that MMP-19 is produced by host mesenchymal cells but not by endothelial capillary cells or CD11b-positive inflammatory cells. Based on a new computer-assisted method of quantification, we provide evidence that host MMP-19 deficiency was associated with an increased early angiogenic response. In addition, increased tumor invasion was observed in MMP-19-/- mice. We conclude that, in contrast to most MMPs that promote tumor progression, MMP-19 is a negative regulator of early steps of tumor angiogenesis and invasion. These data highlight the requirement to understand the individual functions of each NIMP to improve anticancer strategies.