Expression and regulation of stromelysin and matrilysin by growth factors and oncogenes.
Expression and regulation of stromelysin and matrilysin by growth factors and oncogenes.
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生长因子和癌基因对基质溶解素和基质溶解素的表达和调节。
DOI：
10.1042/bst0220058
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发表时间：
1994
影响因子：
3.9
通讯作者：
Matrisian,LM
中科院分区：
文献类型：
--
作者：
McDonnell,S;Wright,JH;Gaire,M;Matrisian,LM
恶性细胞的一个主要特征是它们能够侵入周围的正常组织并转移到身体的远处部位。恶性细胞的转移性对临床医生的治疗提出了最大的挑战，因为肿瘤不再局限于某一区域。肿瘤侵袭和转移的过程极其复杂，涉及一系列连续的步骤，其中许多步骤我们现在可以开始在细胞和分子水平上详细探索。这是一个艰巨的、多步骤的过程，其中只有一小部分肿瘤细胞能够存活并形成新的肿瘤。首先，细胞与原发肿瘤分离并进入滋养它的血管。然后它们被携带到全身循环中，直到停留在毛细血管床上。在这次旅行中幸存下来的细胞可能会穿透血管细胞壁，侵入周围组织并开始增殖并形成新的肿瘤块。从上述情况可以看出，肿瘤细胞必须在几个点表现出侵袭性：进入和逃离循环以及渗透到正常组织中[11。这种组织屏障的破坏是通过特定酶的合成来实现的，这些酶降解构成组织基底膜和基质成分的细胞外基质的蛋白质。参与细胞外基质蛋白水解降解的蛋白酶主要有四类 [2]：丝氨酸蛋白酶、半胱氨酸蛋白酶、天冬氨酰蛋白酶和金属蛋白酶。一般认为这些酶降解肿瘤细胞侵入的局部组织，并且在肿瘤细胞从血管外渗过程中也可能参与穿透基底膜[3, 4]。所用缩写：MMP，基质金属蛋白酶； TIMP，金属蛋白酶组织抑制剂； DMBA，二甲基苯[a]蒽； PMA、佛波醇12-肉豆蔻酸酯13-乙酸酯； TRE、TPA响应元件； AP-1，激活蛋白-1； TIE、TGF-/3、抑制元件； EGF，表皮生长因子； PEA-3，多瘤增强子A结合蛋白-3。
A major characteristic of malignant cells is their ability to invade the normal tissues surrounding them and metastasize to distant sites in the body. It is the metastatic nature of malignant cells that presents the greatest challenge to clinicians in terms of treatment, since the tumour is no longer localized to one area. The process of tumour invasion and metastasis is extremely complex and involves a series of sequential steps, many of which we can now begin to explore in detail at the cellular and molecular level. It is an arduous, multistep process in which only a small proportion of the tumour cells survive to start a new tumour. First, cells detach from the primary tumour and move into the blood vessels that nourish it. They are then carried in the general circulation until they lodge in a capillary bed. Cells that survive this trip may then penetrate the blood vessel cell wall, invade the surrounding tissues and begin to proliferate and form a new tumour mass. As can be seen from the above scenario, tumour cells must manifest invasive properties at several points: to enter and escape the circulation and to penetrate into normal tissues [11. This breaking down of tissue barriers is accomplished by the elaboration of specific enzymes which degrade the proteins of the extracellular matrix that make up basement membranes and stromal components of tissues. There are four main classes of proteases involved in proteolytic degradation of the extracellular matrix [2]: serine proteases, cysteine proteases, aspartyl proteases and metalloproteinases. It is generally thought that these enzymes degrade local tissues through which tumour cells invade, and that they may also be involved in penetration through the basement membrane during the extravasation of tumour cells from blood vessels [3, 4].Abbreviations used: MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase; DMBA, dimethylbenz [a] anthracene; PMA, phorbol 12-myristate 13-acetate; TRE, TPA responsive element; AP-1, activa-tor protein-1; TIE, TGF-/3, inhibitory element; EGF, epi-dermal growth factor; PEA-3, polyoma enhancer A binding protein-3.