Lindsay C K, Thorgeirsson U P
Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892, USA.
Clin Exp Metastasis. 1995 Sep;13(5):381-8. doi: 10.1007/BF00121914.
Studies of tissue inhibitors of metalloproteinases (TIMPs) suggest that one of their main functions is to inhibit metalloproteinase (MMP) activity and thus prevent tumor invasion by preserving extracellular matrix (ECM) integrity. In the present study we examined the distribution of transcripts for TIMP-1, MMP-2 and MMP-9 in monkey hepatocellular carcinoma tissues. In situ hybridization demonstrated elevated levels of TIMP-1 transcripts in fibrous tissue septa, tumor inflammatory infiltrate, tumor blood vessels and in expanded portal areas. However, elevated transcripts for MMP-2 and MMP-9 were found only in tumor inflammatory infiltrate. In lung metastasis high levels of TIMP-1 transcripts were found in the stromal cells surrounding necrotic tumor nodules, in tumor blood vessels, and in mesothelial cells. MMP-9 transcripts were elevated at the periphery of the necrotic tumor nodules. These findings suggest that TIMP-1 and type IV collagenases/gelatinases can be independently regulated in vivo and that TIMP-1 may have functions in ECM remodeling which are unrelated to inhibition of MMP activity.
金属蛋白酶组织抑制剂（TIMPs）的研究表明，其主要功能之一是抑制金属蛋白酶（MMP）的活性，从而通过维持细胞外基质（ECM）的完整性来防止肿瘤侵袭。在本研究中，我们检测了TIMP-1、MMP-2和MMP-9转录本在猴肝细胞癌组织中的分布。原位杂交显示，在纤维组织间隔、肿瘤炎性浸润、肿瘤血管和扩大的门管区中，TIMP-1转录本水平升高。然而，仅在肿瘤炎性浸润中发现MMP-2和MMP-9的转录本升高。在肺转移灶中，在坏死肿瘤结节周围的基质细胞、肿瘤血管和间皮细胞中发现高水平的TIMP-1转录本。在坏死肿瘤结节的周边，MMP-9转录本升高。这些发现表明，TIMP-1和IV型胶原酶/明胶酶在体内可被独立调节，并且TIMP-1可能在ECM重塑中具有与抑制MMP活性无关的功能。
