The first trimester human trophoblast cell line ACH-3P: a novel tool to study autocrine/paracrine regulatory loops of human trophoblast subpopulations--TNF-alpha stimulates MMP15 expression

妊娠早期人类滋养层细胞系 ACH-3P:研究人类滋养层亚群自分泌/旁分泌调节环路的新工具 - TNF-alpha 刺激 MMP15 表达

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作者:Ursula Hiden, Christian Wadsack, Nicole Prutsch, Martin Gauster, Ursula Weiss, Hans-Georg Frank, Ulrike Schmitz, Christa Fast-Hirsch, Markus Hengstschläger, Andy Pötgens, Angela Rüben, Martin Knöfler, Peter Haslinger, Berthold Huppertz, Martin Bilban, Peter Kaufmann, Gernot Desoye

Background

The trophoblast compartment of the placenta comprises various subpopulations with distinct functions. They interact among each other by secreted signals thus forming autocrine or paracrine regulatory loops. We established a first trimester trophoblast cell line (ACH-3P) by fusion of primary human first trimester trophoblasts (week 12 of gestation) with a human choriocarcinoma cell line (AC1-1).

Conclusion

We conclude that ACH-3P represent a tool to investigate interaction of syngeneic trophoblast subpopulations. These cells are particularly suited for studies into autocrine and paracrine regulation of various aspects of trophoblast function. As an example a novel effect of TNF-alpha on matrix metalloproteinase 15 in HLA-G positive ACH-3P and explants was found.

Results

Expression of trophoblast markers (cytokeratin-7, integrins, matrix metalloproteinases), invasion abilities and transcriptome of ACH-3P closely resembled primary trophoblasts. Morphology, cytogenetics and doubling time was similar to the parental AC1-1 cells. The different subpopulations of trophoblasts e.g., villous and extravillous trophoblasts also exist in ACH-3P cells and can be immuno-separated by HLA-G surface expression. HLA-G positive ACH-3P display pseudopodia and a stronger expression of extravillous trophoblast markers. Higher expression of insulin-like growth factor II receptor and human chorionic gonadotropin represents the basis for the known autocrine stimulation of extravillous trophoblasts.

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