Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4-deficient intestinal adenocarcinomas
Matrix metalloproteinase 7 is required for tumor formation, but dispensable for invasion and fibrosis in SMAD4-deficient intestinal adenocarcinomas
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DOI：
10.1038/labinvest.2008.107
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发表时间：
2009-01-01
影响因子：
5
通讯作者：
Taketo, Makoto M.
中科院分区：
文献类型：
--
作者：
Kitamura, Takanori;Biyajima, Kyoko;Taketo, Makoto M.
基质金属蛋白酶7（MMP 7）在人类结直肠癌中表达增加，并与恶性进展相关。然而，其在结肠癌发病机制中的作用尚未完全了解。为了研究MMP 7在结肠癌进展中的作用，我们将Mmp 7敲除突变引入cis-Apc/Smad 4突变小鼠，这是一种侵袭性结肠癌模型，其中SMAD 4依赖性TGF-β家族信号转导被灭活。我们在这里证明，MMP 7的缺乏减少了cis-Apc/Smad 4小鼠肿瘤的数量和大小。另一方面，MMP 7缺陷不影响肿瘤侵袭的深度、基质成纤维细胞的数量或肿瘤中细胞外基质组分的水平。这些结果表明，MMP 7是肿瘤形成所需的，但不是SMAD 4依赖性TGF-β B家族信号传导被阻断的结肠癌的侵袭或纤维化所需的。
Expression of matrix metalloproteinase 7 (MMP7) is increased in the human colorectal carcinomas, and correlates with malignant progression. However, its contribution to colon cancer pathogenesis is not understood thoroughly. To investigate the roles of MMP7 in colon cancer progression, we introduced an Mmp7 knockout mutation into the cis-Apc/Smad4 mutant mouse, a model of invasive colon cancer in which SMAD4-dependent TGF-beta family signaling is inactivated. We demonstrate here that lack of MMP7 reduces the number and size of tumors in the cis-Apc/Smad4 mice. On the other hand, MMP7-deficiency does not affect the depth of tumor invasion, number of stromal fibroblasts or levels of extracellular matrix components in the tumors. These results indicate that MMP7 is required for tumor formation, but not for the invasion or fibrosis of the colon cancer whose SMAD4-dependent TGF-beta b family signaling is blocked.