Expression and importance of matrix metalloproteinase 2 and 9 MMP-2 and -9 in human trophoblast invasionReportar como inadecuado




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Reproductive Biology and Endocrinology

, 2:59

First Online: 04 August 2004Received: 06 May 2004Accepted: 04 August 2004

Abstract

BackgroundThe aim of this study was to examine the invasiveness of first trimester trophoblasts according to the secretion profile of MMP-2 and -9 at different gestational stages, and to test the similarity between primary trophoblast cell-culture and the JAR choriocarcinoma cell-line.

MethodsFirst trimester trophoblasts were divided into two groups: 6–8 weeks early and 9–12 w late of gestation. The two trophoblast groups and JAR cells were cultured in medium, with various concentrations of forskolin and Epidermal Growth Factor EGF. Proteolytic activity was detected by zymography and invasiveness was assessed by Matrigel invasion assay. Student-s T-test was used for statistical analysis.

ResultsIn 6–8 w trophoblast, proMMP-2 was only slightly dominant over proMMP-9 53.2% vs. 46.8% respectively, whereas in 9–12 w, proMMP-9 was clearly dominant over proMMP-2 61.7% vs.38.3% respectively. In JAR cells proMMP-2 was strongly dominant 90.2% vs.9.8% respectively. In JAR cells forskolin significantly increased proMMP-2 and -9 secretion 128.5% +- 12 and 183.2% +- 27.9 of control, respectively. EGF had a dual effect on JAR cells: at 8 ng-ml both proMMP-2 and -9 were increased 133.5% +-15 and 223.9% +- 32.4 of control, respectively while at 80 ng-ml both proMMP-2 and -9 were decreased 65.1% +- 18.3 and 66.6% +- 37 of control, respectively. Forskolin significantly increased both proMMP-2 and -9 secretion in 6–8 w and 9–12 w trophoblasts 125.9% +- 6.3,128.4% +- 6.4; 169.7% +- 20.3, 120.3% +- 4.5 of control, respectively. EGF also significantly increased both proMMP-2 and -9 secretion in 6–8 w and 9–12 w trophoblasts 141.22% +- 14.8, 138.8% +- 10.3; 168.3% +- 18.2, 117.3 +- 3.8 of control, respectively. Both forskolin and EGF increased trophoblast cells invasiveness in all groups. The invasive ability of trophoblast cells, induced by forskolin, was reduced by MMP-2 antibody in: JAR cells, 6–8 w and 9–12 w trophoblasts. Likewise trophoblast invasion induced by EGF was reduced by MMP-2 antibody in all groups. However the invasive ability induced by forskolin or EGF was inhibited by MMP-9 antibody only in trophoblasts from 9–12 w.

ConclusionsFirst trimester trophoblasts express differential gelatinase secretion profile according to the gestational week. In JAR and early trophoblasts 6–8 w MMP-2 is the main gelatinase and the key enzyme in trophoblast invasion. Thereafter in late first trimester trophoblasts 9–12 w, both MMP-2 and -9 participate in trophoblast invasion.

Electronic supplementary materialThe online version of this article doi:10.1186-1477-7827-2-59 contains supplementary material, which is available to authorized users.

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Autor: Elsebeth Staun-Ram - Shlomit Goldman - Diana Gabarin - Eliezer Shalev

Fuente: https://link.springer.com/







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