Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas
Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas
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DOI：
10.1172/jci200215051
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发表时间：
2002-06-01
影响因子：
15.9
通讯作者：
Leach, SD
中科院分区：
文献类型：
--
作者：
Crawford, HC;Scoggins, CR;Leach, SD
在胃肠道上皮中，优势细胞类型之间的化生转化与瘤变的风险增加有关。然而，调节成人上皮化生转变的机制在很大程度上是不明确的。本研究表明基质金属蛋白酶-7 （MMP-7）不仅在大多数人胰腺导管腺癌标本中表达，而且在人和小鼠的胰腺上皮内瘤变和化生管病变中也表达。在胰腺腺泡到导管化生的小鼠模型中，MMP-7在化生转变过程中逐渐积累，导致Fas配体（FasL）的溶解性随之增加。在相同的条件下，缺乏MMP-7或携带失活FasL基因的小鼠在进行性化生和腺泡细胞凋亡的发展中受到严重抑制。因此，MMP-7和FasL影响胰腺上皮化生事件的发生和维持，解释了胰腺和其他胃肠道组织中化生与凋亡之间的联系。
In gastrointestinal epithelium, metaplastic conversion between predominant cell types is associated with an increased risk of neoplasia. However, the mechanisms regulating metaplastic transitions in adult epithelia are largely undefined. Here we show that matrix metalloproteinase-7 (MMP-7) is expressed not only in the majority of human pancreatic ductal adenocarcinoma specimens, but also in human pancreatic intraepithelial neoplasia and metaplastic duct lesions in human and mouse. In a mouse model of pancreatic acinar-to-ductal metaplasia, MMP-7 progressively accumulates during the metaplastic transition, resulting in a concomitant increase in solubilization of Fas ligand (FasL). Under identical conditions, mice either deficient in MMP-7 or carrying an inactive FasL gene are severely inhibited in development of progressive metaplasia and acinar cell apoptosis. Thus, MMP-7 and FasL influence the initiation and maintenance of metaplastic events in pancreatic epithelium, explaining the observed link between metaplasia and apoptosis in pancreas and other gastrointestinal tissues.