Expression of collagenase-3 (MMP-13) enhances invasion of human fibrosarcoma HT-1080 cells
Expression of collagenase-3 (MMP-13) enhances invasion of human fibrosarcoma HT-1080 cells
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DOI：
10.1002/ijc.1619
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发表时间：
2002-01-20
影响因子：
6.4
通讯作者：
Kähäri, VM
中科院分区：
文献类型：
--
作者：
Ala-Aho, R;Johansson, N;Kähäri, VM
胶原酶-3(MMP13)具有特殊的底物特异性和限制性表达。基质金属蛋白酶-13是恶性肿瘤中为数不多的主要由肿瘤细胞表达的基质金属蛋白酶，其表达与肿瘤的侵袭能力密切相关。在本研究中，我们构建了携带人基质金属蛋白酶-13基因的表达载体和重组腺病毒，以探讨基质金属蛋白酶-13在肿瘤细胞侵袭中的作用。我们的结果表明，稳定表达MMP13表达载体或转导MMP13腺病毒的HT-1080细胞通过I型胶原和重组基底膜(Matrigel)显著增加其侵袭能力，而对胶原酶-I(MMP1)、明胶酶A(MMP2)或明胶酶B(MMP9)的表达或激活没有影响。基质金属蛋白酶抑制剂Batimastat(BB-94)和金属蛋白酶组织抑制因子-3(TIMP-3)可阻断表达MMP13的HT-1080细胞侵袭能力的增强，其作用依赖于MMPs的活性。我们的研究结果为基质金属蛋白酶-13作为一种有效的侵袭性蛋白水解酶的作用提供了直接证据，这种酶本身就可以增强癌细胞穿透基底膜和纤维状胶原的能力。(C)2002年Wiley-Liss，Inc.
Collagenase-3 (MMP-13) is characterized by an exceptionally wide substrate specificity and restricted expression. MMP-13 is I of the few MMPs primarily expressed by tumor cells in malignant tumors, e.g., squamous cell carcinomas and its expression correlates with their invasion capacity. In this work, we have constructed an expression vector and a recombinant adenovirus harboring human MMP-13 cDNA to investigate the role of MMP-13 in cancer cell invasion. Our results show that constitutive expression of MMP-13 by HT-1080 cells stably transfected with MMP-13 expression vector or transduced with MMP-13 adenovirus markedly increased their invasion both through type I collagen and reconstituted basement membrane (Matrigel) with no alterations in expression or activation of collagenase-I (MMP-1), gelatinase-A (MMP-2), or gelatinase-B (MMP-9). The enhanced invasion capacity of MMP-13 expressing HT-1080 cells was dependent on MMP activity, as it was blocked by MMP inhibitor Batimastat (BB-94) and tissue inhibitor of metalloproteinases-3 (TIMP-3). Our data provide direct evidence for the role of MMP-13 as a potent invasion proteinase, which alone can enhance the ability of malignant cells to penetrate through both basement membrane and fibrillar collagen. (C) 2002 Wiley-Liss, Inc.