Bischof P
Department Obstetrics & Gynaecology, University of Geneva, Switzerland.
Early Pregnancy (Cherry Hill). 2001 Jan;5(1):30-1.
Gelatinase A and B (MMP-2 and MMP-9) are secreted by cytotrophoblast (CTB); these enzymes digest the major constituents of the endometrial extracellular matrices (ECM). Direct evidence links the expression of MMPs to the metastatic phenotype of tumour cells and tissue inhibitor of metalloproteinases (TIMP) to the inhibition of metastatisation. Gelatinase B (MMP-9, and no other MMP) has been shown in vitro to mediate CTB invasion. ECM components are known to influence adhesion, spreading, migration and differentiation of cells through specific cell surface receptors called integrins. While CTB migrate from the villous into the decidua they modulate their integrin repertoire, secrete MMP-9 and acquire the capacity to digest their environment. Although CTB behave like metastatic cells, in vivo they are only transiently invasive (first trimester) and their invasion is essentially limited to the endometrium and to the proximal myometrium. This temporal and spatial regulation seems to be mediated in a paracrine way by uterine factors and in an autocrine way by trophoblastic factors. We investigated the effects of endometrial regulators such as leukaemia inhibitory factor (LIF), tumour necrosis factor (TNF), transforming growth factor beta (TGFb), interleukin-1 and 6 (IL-1, IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1) as well as trophoblastic factors such as hCG and leptin. All these factors markedly influenced the secretion and/or activation of MMP-2 and MMP-9. Most cytokines influence cell behaviour by modulating phosphorylation of transcription factors. Among these we identified two oncogene products (Jun and Fos) which were activated by TNF or phorbol esters and which promoted the synthesis of MMP-9. We conclude that decidual and trophoblastic products are autocrine or paracrine regulators of trophoblastic invasion of the endometrium and that some of these products act by activating the transcription of early response genes such as transcription factors.
明胶酶A和B（基质金属蛋白酶-2和基质金属蛋白酶-9）由细胞滋养层细胞（CTB）分泌；这些酶可消化子宫内膜细胞外基质（ECM）的主要成分。直接证据表明基质金属蛋白酶的表达与肿瘤细胞的转移表型相关，而金属蛋白酶组织抑制剂（TIMP）与转移抑制相关。已证实在体外明胶酶B（基质金属蛋白酶-9，而非其他基质金属蛋白酶）介导细胞滋养层细胞的侵袭。已知细胞外基质成分通过称为整合素的特定细胞表面受体影响细胞的黏附、铺展、迁移和分化。当细胞滋养层细胞从绒毛迁移至蜕膜时，它们会调节其整合素库，分泌基质金属蛋白酶-9并获得消化其周围环境的能力。尽管细胞滋养层细胞表现得像转移细胞，但在体内它们仅在孕早期具有短暂侵袭性，并且其侵袭基本上仅限于子宫内膜和子宫肌层近端。这种时空调节似乎以旁分泌方式由子宫因子介导，以自分泌方式由滋养层因子介导。我们研究了子宫内膜调节因子如白血病抑制因子（LIF）、肿瘤坏死因子（TNF）、转化生长因子β（TGFβ）、白细胞介素-1和6（IL-1、IL-6）以及胰岛素样生长因子结合蛋白-1（IGFBP-1）的作用，以及滋养层因子如人绒毛膜促性腺激素（hCG）和瘦素的作用。所有这些因子均显著影响基质金属蛋白酶-2和基质金属蛋白酶-9的分泌和/或激活。大多数细胞因子通过调节转录因子的磷酸化来影响细胞行为。在这些因子中，我们鉴定出两种癌基因产物（Jun和Fos），它们被TNF或佛波酯激活，并促进基质金属蛋白酶-9的合成。我们得出结论，蜕膜和滋养层产物是子宫内膜滋养层侵袭的自分泌或旁分泌调节因子，并且其中一些产物通过激活早期反应基因如转录因子的转录发挥作用。
