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.
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).


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.


CONCLUSIONS
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.
Hiden
Ursula
U
Department of Obstetrics and Gynecology, Medical University Graz, Austria. ursula.hiden@klinikum-graz.at
Wadsack
Christian
C
Prutsch
Nicole
N
Gauster
Martin
M
Weiss
Ursula
U
Frank
Hans-Georg
HG
Schmitz
Ulrike
U
Fast-Hirsch
Christa
C
Hengstschläger
Markus
M
Pötgens
Andy
A
Rüben
Angela
A
Knöfler
Martin
M
Haslinger
Peter
P
Huppertz
Berthold
B
Bilban
Martin
M
Kaufmann
Peter
P
Desoye
Gernot
G
D019898:Autocrine Communication; D002459:Cell Fusion; D002460:Cell Line; D045744:Cell Line, Tumor; D002469:Cell Separation; D002822:Choriocarcinoma; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053517:Matrix Metalloproteinase 15 / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D006063:Chorionic Gonadotropin; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C507098:MMP15 protein, human; D014409:Tumor Necrosis Factor-alpha; D053517:Matrix Metalloproteinase 15